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Validated All-in-One™ qPCR Primer for APP(NM_201413.2) Search again
Product ID:
HQP009579
(click here to view gene annotation page)
Powered by BiozSpecies:
Human
Symbol:
Alias:
AAA, ABETA, ABPP, AD1, APPI, CTFgamma, CVAP, PN-II, PN2, alpha-sAPP, preA4
Gene Description:
amyloid beta precursor protein
Target Gene Accession:
NM_201413.2(click here to view gene page)
Estimated Delivery:
Approximately 1-3 weeks, but may vary. Please email sales@genecopoeia.com or call 301-762-0888 to confirm ETA.
Important Note:
By default, qPCR primer pairs are designed to measure the expression level of the splice variant (accession number) you selected for this gene WITHOUT consideration of other possible variants of this gene. If this gene has multiple variants, and you would like to measure the expression levels of one particular variant, multiple variants, or all variants, please contact us for a custom service project at inquiry@genecopoeia.com.
Summary
This gene encodes a cell surface receptor and transmembrane precursor protein that is cleaved by secretases to form a number of peptides. Some of these peptides are secreted and can bind to the acetyltransferase complex APBB1/TIP60 to promote transcriptional activation, while others form the protein basis of the amyloid plaques found in the brains of patients with Alzheimer disease. Mutations in this gene have been implicated in autosomal dominant Alzheimer disease and cerebroarterial amyloidosis (cerebral amyloid angiopathy). Multiple transcript variants encoding several different isoforms have been found for this gene.
Gene References into function
- Kunitz protease inhibitor (KPI) domain forms of APP regulate extracellular cleavage of secreted APP by inhibiting the activity of a secreted APP-degrading protease
- Alzheimer's Amyloid-beta peptide contains catalase binding site and inhibits anti-oxidant activity
- Mutations in APP may predispose to very-late-onset Alzheimer disease.
- helix-containing intermediates in amyloid beta-protein fibrillogenesis
- Serine phosphorylation site within the Alzheimer's Amyloid-beta sequence
- Here the technique of small angle neutron scattering has been used to determine the structure of these Abeta micelles
- Insulin-degrading enzyme rapidly removes the beta-amyloid precursor protein intracellular domain (AICD).
- Estrogen lowers Alzheimer beta-amyloid generation by stimulating trans-Golgi network vesicle biogenesis
- a biomarker for Alzheimer disease
- Tyrosine phosphorylation of the beta-amyloid precursor protein cytoplasmic tail promotes interaction with Shc.
- mitochondrial dysfunction in Down's syndrome may lead to intracellular deposition of Abeta42, reduced levels of AbetaPPs, and a chronic state of increased neuronal vulnerability.
- early signaling mechanisms involved in Abeta toxicity using the SH-SY5Y neuroblastoma cell line (amyloid beta protein)
- Apolipoprotein E4 potentiates amyloid beta peptide-induced lysosomal leakage and apoptosis in neuronal cells
- Oxidation of methionine 35 attenuates formation of amyloid beta -peptide 1-40 oligomers
- Accelerated plaque accumulation, associative learning deficits, and up-regulation of alpha 7 nicotinic receptor protein in transgenic mice co-expressing mutant human presenilin 1 and amyloid precursor proteins
- binds to G(M1)ganglioside and promotes the soluble amyloid beta protein polymerization
- forms a seed of amyloid beta protein aggregation via binding to G(M1)ganglioside
- natural oligomers of human Abeta are secreted and cerebral microinjection of cell medium containing these oligomers and abundant Abeta monomers but no amyloid fibrils markedly inhibited hippocampal long-term potentiation in rats (amyloid beta protein).
- Activation of Cyclin-Dependent-Kinase-1 by Alzheimer's Amyloid-beta peptide
- Munc18a acts through direct and indirect interactions with X11 proteins and powerfully regulates APP metabolism and Abeta secretion.
- A second locus for very-late-onset Alzheimer disease: a genome scan reveals linkage to 20p and epistasis between 20p and the amyloid precursor protein region.
- results show that the constrained decapeptide dimers rapidly form an intramolecular, antiparallel beta-sheet and polymerize into amyloid fibrils at low concentrations
- Alzheimer abeta peptide: carboxy terminus influences conformation, aggregation, and neurotoxic properties.
- gamma secretase cleavage of APP may contribute to Alzheimer's disease-related neurodegeneration [GAMMA SECRETASE]
- Rac1 generates reactive oxygen species through beta-amyloid signaling
- mutation of leucin 166 in presenilin-1 affects generation independent of effect on Abea 42 production
- Mechanism of membrane depolarization caused by the Alzheimer Abeta1-42 peptide
- Eliminating membrane depolarization caused by the Alzheimer peptide Abeta(1-42, aggr.).
- REVIEW: the folding pathways of an Alzheimer's amyloid Abeta-Peptide explored by long time dynamic simulations.
- Mutations that reduce aggregation of the Alzheimer's Abeta42 peptide: an unbiased search for the sequence determinants of Abeta amyloidogenesis.
- [alpha]-Secretase ADAM10 as well as [alpha]APPs is reduced in platelets and CSF of Alzheimer disease patients.
- Profile of cholesterol-related sterols in aged amyloid precursor protein transgenic mouse brain
- Transcriptional activation and increase in expression of Alzheimer's beta-amyloid precursor protein gene is mediated by TGF-beta in normal human astrocytes
- Transforming growth factor-beta-induced transcription of the Alzheimer beta-amyloid precursor protein gene involves interaction between the CTCF-complex and Smads
- description of APP binding site for fibrillar Abeta and identification by alanine scanning mutagenesis
- mutations in PSEN1 increase Abeta42 production
- mutant proteins form annular protofibrils (similar to pore-forming bacterial toxins), suggesting that inappropriate membrane permeabilization might be the cause of cell dysfunction and even cell death in amyloid diseases, as Alzheimers and Parkinsons
- Human APP expressed in rat cortical cell neurons in culture is processed to produce amyloid beta and soluible APP. Expression of APP triggers neuronal cell death.
- laminin affects polymerization, depolymerization and neurotoxicity of this protein.
- Several months after intracerebral injections of this protein into betaAPP transgenic mice, cerebral beta-amyloidosis was induced.
- Annexin 5 and apolipoprotein E-2 protect PC12 rat cells against the cytotoxicity of this protein.
- There is a synergetic effect of APP dysfunction, revealed by Abeta aggregation, on the neuron-to-neuron propagation of tau pathology in aging and sporadic Alzheimer's disease.
- Differential rates of frameshift alterations in four repeat sequences of hereditary nonpolyposis colorectal cancer tumors.These repeats consisted of (A)10 in the TGF beta RII, (G)8 in the BAX, (A)8 in the CASP1, and (CCA)7 in the APP genes.
- Coordination of copper(II) ions by the 11-20 and 11-28 fragments of human and mouse beta-amyloid peptide
- new evidence suggests that the C-terminal cytosolic tail of beta-amyloid precursor protein may have multiple biological activities, ranging from axonal transport to nuclear signaling.
- Amyloid subunits from chromosome 13 dementia brains are able to fully activate the complement cascade at levels comparable to those generated by Abeta1-42
- APOE isoproteins are inefficient at complexing with synthetic Alzheimer disease amyloid beta-protein in vitro.
- Two populations of Abeta (25-35) are detected, one in the aqueous vicinity of the membrane surface and the second inside the hydrophobic core of the lipid membrane
- With vesicles mimicking neuronal membranes, both Abeta29-42 unprotected and Abeta29-42 N-protected peptides have similar capacity to induce membrane fusion and permeabilization; the N-terminus is not crucial for the peptide destabilizing properties.
- Two genetic variants, a common +37G/C polymorphism and a rare -9G/C variant, have been identified and characterized in the core sequences of the proximal APP promoter.
- Presenilin-1 regulation of beta APP trafficking may represent an alternative mechanism by which FAD-linked PS1 variants modulate beta APP processing.
- Abeta accumulation in the brain is limited by endothelin-converting enzymes 1 and 2
- These results demonstrate that late Simian virus 40 transcription factor activation is required for the neuroprotective effects of amyloid precursor protein via phosphoinositide 3-kinase/Akt signalling.
- role of MEF2 in the anti-apoptotic signaling pathways activated by APP; model of anti-apoptotic APP signaling is proposed where APP mediates p38 MAPK-dependent phosphorylation and activation of MEF2
- Mutation has pathogenic effects in cerebral amyloid angiopathy. (REVIEW)
- the termini of Abeta1-40 and Abeta1-42 peptides are generated by a process involving presenilin 1
- the effect and the mechanism of fluorinated alcohols on the amyloid beta-to-alpha conversion
- the decapeptide region of APP is likely an active site-directed inhibitor that has high selectivity toward gelatinase A
- APP copper binding domain (CuBD) contains a novel copper binding site that favors Cu(I) coordination
- Abeta production in astrocytes is potentiated by TGF-beta1
- Data indicated that variation of amyloid precursor protein (APP) gene expression in peripheral blood mononuclear cells might be a pathogenic source of Alzheimer's disease.
- APP is cleaved by a process that involves PDGF and beta-gamma-secretase through a Src-Rac-dependent pathway
- The transcriptional activity of the APP intracellular domain-Fe65 complex is inhibited by activation of the NF-kappaB pathway.
- after A beta binds to raft-like membranes composed of monosialoganglioside GM1/cholesterol/sphingomyelin (1/1/1), the protein can translocate to the phosphatidylcholine membranes to which soluble A beta does not bind
- results show that neuronal activity regulates the production and secretion of Abeta by controlling APP processing; also report that Abeta modulates synaptic strength
- 3D reconstruction of beta-amyloid in the hippocampus and entorhinal cortex of PDAPP transgenic mice
- soluble oligomers have a unique distribution in Alzheimer disease brain that is distinct from fibrillar amyloid
- factors that affect both nucleation and elongation in the formation of highly toxic forms of Abeta aggregates
- Alzheimer's disease-linked Swedish amyloid precursor protein mutation causes oxidative stress, and affects caspases and the JNK pathway
- LXR and ABCA1-induced changes in membrane lipid organization have favorable effects on processing of APP
- anterior pharynx defective 1B-like, anterior pharynx defective 1A, presenilin enhancer 2, and nicastrin increase amyloid beta peptide levels.
- conformational plasticity may play a role in allowing APP to interact with a number of distinct physiological ligands
- Release of APP intracellular domain from the membrane takes place in a compartment downstream of the endoplasmic reticulum, is dependent on presenilin proteins, and can be inhibited by treatment with established gamma-secretase inhibitors.
- Nornicotine covalently alters the amyloid beta peptide 1-40, leading to reduced peptide aggregation, reduced plaque formation, altered clearance, & attenuated toxicity of soluble aggregates
- REVIEW: pathways involved in proteolytic processing of APP which could contribute to some of the age-related changes seen in Alzheimer's disease
- Patients with high Abeta1-42 levels had more cholinergic dystrophic neurites in the plaques than cases with lower Abeta1-42. Abeta1-42 may also trigger cholinergic dysfunction by promoting aberrant neuritic sprouting.
- APP and Fe65 mediate transactivation with low density lipoprotein receptor-related protein
- kinesin-I-dependent neuronal AbetaPP transport, which controls AbetaPP processing, may be regulated by JIP1
- A beta or hydrogen peroxide (H(2)O(2)) induces oxidative stress and cell cytotoxicity. The exposure of cells to A beta results in an increased trk B expression with a concurrent reduction in truncated trk B levels
- Unexpectedly, the frameshifted APP+1 level in the CSF of non-demented controls was much higher (1.75 ng/ml) than in the CSF of Alzheimer patients.
- Threonine 668 within the Amyloid beta protein precursor intracellular domain is indeed phosphorylated by JNK1; JIP-1 only facilitated phosphorylation of AbetaPP but not of the two other family members APLP1 (amyloid precursor-like protein 1) and APLP2
- ABETA in neutral aqueous solution is characterized variously as a random coil or a heterogeneous mixture. At lower pH, a different conformation is favored. The reactivity of the monoclonal antibody 6F/3D is drastically reduced.
- beta-sheet content of Abeta mutants correlates with their aggregation and role in cerebral amyloid angiopathy
- The soluble amino-terminal ectodomain of beta-amyloid precursor protein regulates dendrite motility and melanin release in epidermal melanocytes and melanoma cells.
- Notch1 competes with the amyloid precursor protein for gamma-secretase
- an increase in the ratio of Abeta(WT)/Abeta(MUT(Arctic)) may result in the accumulation of potential neurotoxic protofibrils and acceleration of disease progression in familial Alzheimer's disease mutation carriers
- expression of COX-1 and COX-2 may influence Amyloid beta peptide generation through mechanisms that involve PG-E2-mediated potentiation of gamma-secretase activity
- CSF-Abeta1-42 showed no additional benefit in discriminating AD patients from controls but might be useful for tracking the severity of the disease.
- endogenous A beta can be produced directly at the plasma membrane and alterations in the degree of APP endocytosis may help regulate its production
- FE65L1 potentiates gamma-secretase processing of APP CTFs. This requires binding of FE65L1 to APP and APP CTFs. Enhanced APP CTF processing can be detected in early endosome vesicles
- Amyloid beta peptide (Abeta42) activates PLC-delta1 promoter through the NF-kappaB binding site
- Rho and its effector, Rho-associated kinase, preferentially regulated the amount of Abeta42 produced in vitro and only NSAIDs effective as Rho inhibitors lowered Abeta42
- By NMR studies, supramolecular organization of beta-sheets in amyloid fibrils is determined by a sensitive balance of multiple side-chain-side-chain interactions
- Local quinolinic acid production induced by aggregated amyloid peptide Abeta1-42 may be one of the factors involved in the pathogenesis of neuronal damage in Alzheimer's disease.
- Patients who progressed to dementia of Alzheimer type at 2-year follow-up showed significant decrease of baseline platelet APP compared with stable mild cognitive impairment patients and patients who developed other types of dementia
- proline scanning data are most compatible with a model for amyloid protofilament structure loosely resembling the parallel beta-helix folding motif, such that each Abeta(15-36) core region occupies a single layer of a prismatic, H-bonded stack of peptide
- Data suggest that the insulin-degrading enzyme-mediated clearance mechanism for endoplasmic reticulum-localized amyloid beta represents an as yet unknown type of degradation which is not entirely dependent on the proteasome.
- the internal structures are similar for beta2-microglobulin and amyloid fibril protein
- APLP1 and APLP2 and APP are processed similarly to act via the same nuclear target and are regulated by BACE 1 in neurons
- beta-amyloid is cross-linked by peroxidase activity of cyclooxygenase-2, which also generates toxic intracellular forms of oligomeric Abeta
- processing of amyloid-beta precursor protein and amyloid-beta deposition are modulated by luteinizing hormone
- Involvement of X11L in the phosphorylation of APP family proteins in cellular stress and suggest that X11L protein may be important in the physiology of APP family proteins as well as in the regulation of Abeta production.
- spectral studies of the mode of Cu(2+) binding to Abeta in solution show that the mode of copper binding is highly pH-dependent & that histidine residues 13, 6, and 14 are involved in Cu(2+) coordination but that Tyr(10) is not.
- Copper depletion down-regulates expression of the Alzheimer's disease amyloid-beta precursor protein gene
- we found a change in the ratio of KPI(+)(containing a Kunitz-type serine protease inhibitor domain ) to KPI(-)(without Kunitz-type serine protease inhibitor domain) mRNA isoforms of APP.
- Presinilin 1 Delta E9 molecules expressed in Spodoptera cells cells retain the ability to modulate amyloid beta protein levels.
- AbetaPP and the AIDA-1 proteins interact in vitro, in living cells and, endogenously, in leukemia cell lines
- Amyloid-beta protein accumulation induces long-term memory impairment and disturbance of the cholinergic system in APPsw transgenic mice.
- a role of the 30-bp proximal APP promoter element in enhanced apoptotic neuronal cell death
- Alcadein and amyloid beta-protein precursor regulates FE65-dependent gene transactivation
- transcriptional transactivation by APP and Notch may involve distinct mechanisms; whereas the Notch intracellular domain directly functions in the nucleus, the AICD acts indirectly by activating Fe65
- Only cells expressing RAGE at the cell surface showed hypersensitivity to Abeta.
- beta-amyloid deposition levels in brain correlate with CD36 expression independent of the occurrence of Alzheimer's disease
- results reveal a new function for sAPP as a regulator of subventricular zone progenitor proliferation in the adult central nervous system
- glypican-1 interacts with polymerized Abeta in detergent-insoluble glycosphingolipid-enriched domains, resulting not only in amyloid deposition in senile plaques of AD brain, but also in accelerating neuronal cell death in response to stress and Abeta
- Presenilin 1 stabilizes the C-terminal fragment(C99) of the amyloid precursor protein independently of gamma-secretase activity.
- Abeta interacts with ABAD in the mitochondria of Alzheimer's disease patients and transgenic mice; data suggest that the ABAD-Abeta interaction may be a therapeutic target in Alzheimer's disease
- N-acetylaspartate, glutamate and glutathione are decreased by 17%, 22% and 36%, respectively, in the cerebral cortex of APP transgenic (APPTg2576) mice at 19 months of age when Abeta deposits are widespread.
- complexed with acetylcholinesterase, is toxic to rat brain beta-amyloid aggregation, laminin expression, reactive astrocytosis, and neuronal cell loss.
- ADAM10 is the major alpha-secretase cleaving APP, with TACE playing a minor role
- There was a 13-year difference in the age at onset of dementia in DS associated with the number of tetranucleotide repeat alleles in APP. APP is an important locus predicting the age at onset of dementia in people with Down syndrome.
- memapsin 2 and APP, immunoprecipitated together from cell lysates, suggested that the interaction of these two proteins is part of the native cellular processes
- results support the hypothesis that Abeta peptide and the oxidative state of Met-35 may be involved in the mechanisms responsible of neurodegeneration in Alzheimer's disease
- The 5'-UTR of human APP contains several interesting control elements, such as an acute box element, a CAGA box (on a stem-loop), an IRE, and a transforming growth factor-beta-responsive element, that could control APP expression & trigger amyloid in AD.
- Amyloid beta-protein stimulated in monocytes the gene expression for sphingosine-1-phosphate receptors 2 and 5, but not 1, 3, or 4.
- Results suggest that the involvement of protein kinase C alpha in carbachol-induced soluble amyloid precursor protein (sAPPalpha) release is negligible, but PKC epsilon may be important in coupling cholinergic receptors with APP metabolism.
- processing of APP by BACE1 is dependent on a mutual structural compatibility in addition to the sequence feature
- Secretion of long Abeta-related peptides processed at epsilon-cleavage site is dependent on the alpha-secretase pre-cutting
- Abeta peptide is secreted into cell medium upon cell death
- Co-expression of APP695 and frame-shifted APP(+1) affects the processing of APP695 in a pro-amyloidogenic way and this could gradually contribute to Alzheimer's disease pathology, as has been implicated in Down's syndrome patients
- The independently folded extracellular domain of amyloid-beta precursor protein (APP) constitutes the C-terminal half of the central extracellular region of APP that has been implicated in the regulation of APP cleavage.
- Abeta engenders a dysfunctional encoding state in neurons and may initiate and/or contribute to cognitive deficit at an early stage of AD before or along with neuronal degeneration.
- Amyloid beta-peptide (Abeta) interaction with low-density lipoprotein receptor-related protein LRP and/or Abeta-induced LRP loss at the blood-brain barrier mediate brain accumulation of neurotoxic Abeta.
- cleavage of APP but not syntaxin 1 is independent of cell surface regulation by extracellular ligands
- Alpha-secretase-cleaved transgenic human APP increases the expression levels of several neuroprotective genes & protects organotypic hippocampal cultures from Abeta-induced tau phosphorylation & neuronal death in mice.
- TNFa, IL-1b and ifn-gamma stimulate gamma-secretase-mediated cleavage of amyloid precursor protein through a JNK-dependent MAPK
- the interaction between AbetaPP and AIDA-1 is regulated by alternative splicing of the AIDA-1 protein
- The A713T mutation may cause AD with cerebral amyloid angiopathy. The mutation is inside the A[beta] sequence & next to the gamma-secretase cleavage site. It may alter APP processing to increase fibrillogenic A[beta]42 or change its properties.
- beta-amyloid and tau-bearing skeletal myotubes show calcium dyshomeostasis
- Data provide functional evidence that APP can perturb intracellular calcium (Ca2+) homeostasis by emptying intracellular Ca2+ stores and triggering Ca2+ entry through store-operated channels in cultured mouse cortical neurons.
- Hyperactivity and impaired learning abilities characterize a model of Alzheimer's disease and cerebral angiopathy in transgenic mice overexpressing the betaAPP gene with the Swedish mutation.
- transgenic mice overexpressing both human BACE1 and APP show specific alterations in APP processing and age-dependent Abeta deposition suggesting that modulation of BACE1 activity may play a significant role in Alzheimer disease pathogenesis
- fibrillar Abeta1-42 peptides induce neuronal apoptosis through the NADPH oxidase-superoxide-hydrogen peroxide-NS-Mase-ceramide pathway
- the hydrophobicity of the C-terminal two residues of Abeta42 is not related to its aggregative ability and neurotoxicity, rather the C-terminal three residues adopt the beta-sheet
- Changes in total CTFgamma levels do not correlate with either increase or decrease of any Abeta species, and inhibition of Abeta-peptide formation starting from position +1 (Abeta1-x) does not affect CTFgamma production.
- Familial Alzheimer's disease mutations affect CTFgamma generation.
- there is a presenilin-dependent zeta-cleavage site within the transmembrane domain of amyloid precursor protein
- A713T in Amyloid A Precursor is implicated in the pathogenesis of Early Onset Alzheimer Disease .
- a defect in Abeta proteolysis by IDE contributes to the accumulation of this peptide in the cortical microvasculature
- Hmgb1 protein high mobility group 1 released from dying neurons may inhibit microglial amyloid beta42 clearance and enhance the neurotoxicity of Amyloid beta42.
- synapse-associated amyloid-beta is prominent in regions relatively unaffected by Alzheimer Disease lesions
- Data describe the processing of beta-secretase (BACE), implicated in Alzheimer's disease through processing of beta-amyloid precursor protein, into smaller metabolites.
- specific role of APP isoforms containing Kunitz protease inhibitor in DLB pathogenesis
- Targeting and functional disruption of particular synapses by Abeta oligomers may provide a molecular basis for the specific loss of memory function in early Alzheimer's disease.
- Active gamma-secretase is present in the plasma membrane. Notch is processed at the cell surface and the majority of APP is processed by intracellular gamma-secretase
- CLA-1 functions as an endocytic SAA receptor and is involved in SAA-mediated cell signaling events associated with the immune-related and inflammatory effects of SAA
- Abeta, especially intracellular Abeta, counteracts the antiapoptotic function of its precursor protein and predisposes cells to p53-mediated, and possibly other, proapoptotic pathways.
- Interaction of human and murine Abeta peptides, Abeta40 and Abeta42. Interspecies Abeta aggregates and fibers are readily formed and are more stable than homogenous human fibers.
- beta-amyloid and APP can oxidize cholesterol to form 7beta-hydroxycholesterol
- Data suggest an important physiological role of APP in the control of JNK/c-Jun signalling, target gene expression and cell death activation in response to cytotoxic stress.
- beta-amyloid peptide fibrils have three distinct binding sites for thioflavin T
- Abeta1-42 may play an important role in the negative regulation of TGF-beta1-induced MMP-2 production via Smad7 expression
- p65FE65 may be an intracellular mediator in a signaling cascade regulating alpha-secretion of APP
- different fibril morphologies of Abeta(1-40) have different underlying molecular structures; structure can be controlled by variations in fibril growth conditions; both morphology & molecular structure are self-propagating
- An APP T174I mutation is associated with early-onset Alzheimer disease in an African American kindred.
- In this mini-review, the role of the cytoplasmic domain of beta-amyloid protein precursor (APP) in APP trafficking and proteolysis is described.
- Data describe a relationship between heparan sulfate and copper binding of amyloid precursor protein (APP) and amyloid precursor-like protein 2 (APLP2) in the modulation of nitroxyl anion-catalyzed heparan sulfate degradation in glypican-1.
- amyloid Ass 1-42 peptide forms insoluble monolayers with high stability against lateral compression
- Overt neuronal cell death mediated by Abeta(1-40) is critically dependent on ongoing Abeta(1-40) polymerization and is not mediated by a single stable species of neurotoxic aggregate.
- The mechanism of Abeta-induced neuronal apoptosis sequentially involves JNK activation, Bcl-w downregulation, and release of mitochondrial Smac, followed by cell death.
- X11alpha and X11beta have roles in beta-amyloid precursor protein processing
- structure-activity correlation of the 1-20 and 1-16 fragments of Alzheimer's disease-related beta-amyloid peptide
- endocytosis of LRP modulates cell surface distribution and processing of the beta-amyloid precursor protein
- Results indicate that alleles of IDE contribute to variability in A beta deposition in the AD brain and suggest that this relationship may have relevance for the degree of cognitive dysfunction in AD patients.
- calcium dysregulation and membrane disruption are ubiquitous neurotoxic mechanisms of soluble amyloid oligomers
- Autoantibodies to redox-modified oligomeric Abeta are attenuated in the plasma of Alzheimer's disease patients
- This study strongly implicates intraneuronal Abeta in the onset of cognitive dysfunction in transgenic 3xTg-AD mice, which develop both amyloid and tangle pathology.
- Soluble oligomers of Abeta induce a profound, early inflammatory response in rat astrocyte cultures, whereas fibrillar Abeta show less increase of pro-inflammatory molecules, consistent with a more chronic form of inflammation.
- analysis of interaction between presenilin 1 and APP (amyloid beta precursor)
- thermodynamic analysis of the nucleation constant rate in beta amyloid fibrillogenesis
- deletion experiments suggested that the last 50 amino acid residues of LRP-soluble tail contain the important domain for altering APP processing and Abeta production
- Of the nine pathogenic mutations found in 12 cases, three were in APP, one in PSEN2, and five in PSEN1, including two novel Greek mutations (L113Q and N135S) in Alzheimer disease
- activation of the G protein-coupled P2Y2 receptor (P2Y2R) subtype expressed in human 1321N1 astrocytoma cells enhanced the release of sAPP alpha in a time- and dose-dependent manner
- mu-calpain, is a potential candidate for alpha-secretase in the regulated APP alpha-processing
- oxidant production in the mitochondrial electron transport chain is a critical factor, acting upstream of amyloid beta peptide production in the up-regulation of Ca(2+) channels in response to chronic hypoxia
- Aberrant accumulation of amyloid beta42 in amyotrophic lateral sclerosis (ALS) spinal cord motor neurons is associated with oxidative stress, and may play a role in the pathogenesis of neurodegeneration in ALS.
- An HtrA1 inhibitor causes accumulation of Abeta in astrocyte cell culture supernatants and colocalizes with beta-amyloid deposits in human brain samples.
- proposed that although CCL2 stimulates mononuclear phagocyte accumulation, it increases Abeta deposition by reducing Abeta clearance through increased apolipoprotein E expression
- the mechanism of IL-1beta-induced-sAPP(alpha) release is dependent on MEK1/2- and JNK-activated alpha-secretase cleavage in neuroglioma U251 cells
- Inheritance of the rs1799724-T TNF-alpha allele appears to synergistically increase the risk of Alzheimer's disease in APOEepsilon4 carriers and is associated with altered CSF Abeta42 levels
- Based on immunoblotting studies of cerebrospinal fluid (CSF) from normals, we find that the bulk of the abetas are bound to the ER chaperones, ERp57 and calreticulin.
- transgenic mice overexpressing wild-type human APP gene (hAPP/+) displayed a much higher expression of FAS. FAS overexpression was reduced in cortex of mice overexpressing both wild-type hAPP gene & wild-type human superoxide dismutase-1 gene.
- glycosphingolipids are implicated in the regulation of the subcellular transport of the beta-amyloid precursor protein
- Altogether, our results demonstrated that phosphorylated CTFs can be the substrates of the gamma-secretase and that an increase in the phosphorylation of APP-CTFs facilitates their processing by gamma-secretase.
- PPARgamma overexpression in cultured cells dramatically reduced Abeta (amyloid-beta) secretion, affecting the expression of the APP (Abeta precursor protein) at a post-transcriptional level.
- increased expression of wild type APP renders neuronal cells more vulnerable to oxidative stress leading to cell death
- The strong negative correlation between net charge and oligomerization indicates that electrostatic repulsion between A beta monomers impedes their association.
- accumulations of intramembranous Abeta peptides might affect the functions of amyloid precursor protein itself and the assembly of the PS1, Aph1, Pen 2, Nicastrin complex in Alzheimer's disease [Perspective article]
- BRI2 gene binds the Alzheimer gene amyloid-beta precursor protein and inhibits amyloid-beta production
- biophysical analysis of amyloid beta-protein at low pH and its protofibril formation
- Site directed mutagenesis of the Alzheimer's Abeta (1-40) peptide to determine the effect of different side chains on the propensity of nucleation.
- Transfected into mice, immunization ameliorates senile plaque formation, in an Alzheimer disease model.
- Beta-amyloid (Abeta) induces a significant decrease in dynamin 1 in hippocampal neurons and in the transgenic 2576 mouse model of Alzheimer's disease
- BRI2 had a modulatory effect on amyloid precursor protein (APP) processing, increasing levels of cellular APP and COOH-terminal fragments while decreasing COOH-terminal fragments and secretion of total APP and Abeta peptides.
- Ultrasonication induces amyloid fibril formation of beta2-microglobulin
- APP can induce postdevelopmental axonal arborization, which depends critically on a conserved motif in the C-terminus and requires interaction with the Abelson (Abl) tyrosine kinase.
- We have studied the effect of alphaB-crystallin on the fibril growth of the Abeta (amyloid beta)-peptides Abeta-(1-40) and Abeta-(1-42).
- properties of the side chains at positions 41 and 42 cause Abeta42 to aggregate more readily than Abeta40
- parenchymal and vascular amyloid deposits in the cerebral cortex are associated with a different array of Abeta peptide species.
- APP is internalized by a dynamin-dependent process, and alterations in the activity of proteins that mediate endocytosis might lead to significant changes in Abeta production
- Results show the effectiveness of ectoine and hydroxyectoine on the inhibition of amyloid beta42 aggregation and toxicity to human neuroblastoma cells.
- REVIEW: The biology, structure and physical properties of Abeta peptides are discussed, as well as existing therapeutics and future strategies for the treatment of Alzheimer's disease
- Herpes virus infection leads to rapid loss of full length APP from neuronal cells.
- These findings challenge the idea that tau pathology in Alzheimer's disease is merely a downstream effect of amyloid production/deposition and suggest that reciprocal interactions between beta-amyloid and tau alterations may take place in vivo.
- Data show that amyloid beta:Cu2+ complexes oxidize cholesterol selectively at the C-3 hydroxyl group, catalytically producing 4-cholesten-3-one and therefore mimicking the activity of cholesterol oxidase.
- Abeta but not tau is deregent-insoluble early in the pathogenesis of Alzheimer's disease
- Abeta(1-42) globulomer is a persistent structural entity formed independently of the fibrillar aggregation pathway
- Abeta40 evokes dose-dependent sodium and calcium ions in unicellular phosphatidylserine liposomes; a small amount of negatively charged phospholipids is sufficient to support the process of ion channel formation.
- A novel mutation (L705V) within the Abeta sequence of AbetaPP in a family with autosomal dominant, recurrent intracerebral hemorrhages.
- data support the presence of a turn structure at positions 22 and 23 in E22K-Abeta42 fibrils; formation of a salt bridge between Lys-22 and Asp-23 in the minor conformer might be a reason why E22K-Abeta42 is more pathogenic than wild-type Abeta42
- Amyloid-beta induces disulfide bonding and aggregation of GAPDH in Alzheimer's disease
- results show apoE co-localized with amyloid beta in amyloid plaques that lack immunoreactivity with antibodies to N-terminal epitopes of amyloid beta indicating that formation of apoE-amyloid beta complexes may conceal N-terminal epitopes of amyloid beta
- in the amyloid beta-protein, the central hydrophobic cluster is particularly important in controlling Abeta40 assembly, whereas the C-terminus plays the more significant role in Abeta42 assembly
- mitochondrial Abeta has a role in neuronal metabolic dysfunction in Alzheimer's disease
- two protected core regions, Glu11-Gly25 and Lys28-Ala42, and that the residues in between, Ser26 and Asn27, as well as those in the N terminus, Asp1-Tyr10, are solvent-accessible, this provides a molecular explanation for the increased amyloidogenicity
- This review describes in detail the different subdomains of APP and assigns functional significance to particular structures identified in the protein.
- an additional hypothesis involving the amyloid-beta peptide and the role of Met-35 has been proposed to clarify the mechanisms responsible of neurodegeneration in Alzheimer's disease.
- mutagenesis and structural analysis of Abeta-(1-40) amyloid fibrils
- Findings show a close association between Abeta deposition and nigrostriatal pathology in transgenic mice and suggest that altered familial Alzheimer's disease-linked amyloid metabolism impairs, at least in part, the function of dopaminergic neurons.
- Transfected into transgenic mice, involved in induction of tau pathology, making the interference of Abeta oligomerization a valid therapeutic target in Alzheimer disease.
- apoE4 and Abeta1-42 may work in concert in neurons to increase lysosome formation while increasing the susceptibility of lysosomal membranes to disruption, release of lysosomal enzymes into the cytosol, and neuronal degeneration.
- analysis of APP region 1-16 structural changes upon zinc binding and in vitro aging
- the phosphorylation of APP regulates the formation of a pAPP-JIP-1 complex that accumulates in neurites independent of nonphosphorylated APP
- age-dependent membrane modification was associated with an altered distribution of PS1 and BACE between detergent-resistant membranes (DRM) and non-DRM fractions, very likely affecting their APP processing potential
- A decrease in presynaptic amyloid precursor protein (APP) and amyloid precursor-like protein 2 (APLP2) leads to a decrease in stimulus-driven synaptic activity.
- Soluble forms of amyloid beta (Abeta1-42) induce actin-containing rods in brains of transgenic Alzheimer mice; these stalled vesicles provide a site for producing Abeta(1-42), inducing more rods and expanding the degenerative zone.
- apoE4 appears to modulate APP processing and Abeta production through both the low-density lipoprotein receptor-related protein pathway and domain interaction
- APLP1 affects the endocytosis of APP and makes more APP available for alpha-secretase cleavage
- Review. The most basic soluble Abeta peptides are stable dimers with hydrophobic regions. They perturb metabolic processes, cause release of harmful reactive compounds, reduce blood flow, induce mitochondrial apoptotic toxicity & inhibit angiogenesis.
- Amyloid-beta precursor protein (APP) processing pathways are critical for cognitive, emotional, and synaptic functions
- In cells stably overexpressing the functional PAC1 receptors, PACAP-27 & PACAP-38 strongly stimulated alpha-secretase cleavage of APP.
- SorLA acts as a trafficking receptor that prevents beta-site APP-cleaving enzyme interactions with amyloid precursor protein & hence BACE cleavage of APP.
- Review. Current knowledge on APP trafficking and amyloidogenic processing of APP in intracellular membrane compartments and microdomains is reviewed.
- a cell-cell interaction occurs in the production of beta-amyloid in cell cultures
- the neurotoxic Abeta amyloids 1-40 and 1-42, related to Alzheimer's disease, spontaneously enter the membranes of intact erythrocytes and cause their lysis but Abeta 1-38 and Abeta 1-35, which are not neurotoxic, have no observable effects on erythrocyte
- Results show that purified human HDL and recombinant apolipoprotein A-I lipid particles bind directly to amyloid beta and apolipoprotein C-II amyloid fibrils.
- release of Abeta- or Nbeta-like peptides is a common feature of the proteolysis during regulated intramembrane proteolysis signaling
- Data for the two main isoforms of the soluble extracellular domain of amyloid precursor protein (APP; sAPPalpha(695) and sAPPalpha(770)) provided models of sufficiently high resolution to identify distinct structural domains of APP.
- Lower BACE transcription is responsible for the minority of APP undergoing the amyloidogenic pathway and relatively lower Abeta production in the normal conditions, and that a slight increase in BACE1 can induce a dramatic elevation in Abeta production.
- Abeta and hyperphosphorylated tau formation in somatostatin cells are basically independent events Decreased somatostatin only partly goes together with cytoskeletal changes in somatostatin cells in nucleus tuberalis lateralis of Alzheimer's disease.
- first evidence that chronic stress accelerates the onset and severity of cognitive deficits and that these are highly correlated with pathological changes, as APP deposition.
- role of APP in activation of gene transcription; findings show that antibody-bound APP induces expression of ornithine decarboxylase
- flotillin-1 may recruit APP to lipid rafts and therefore participate in the localization and processing of APP
- HspB8 might play important role in regulating Abeta aggregation and, therefore, development of classic senile plaques in Alzheimer's disease and cerebral amyloid angiopathy in hereditary cerebral hemorrhage with amyloidosis of Dutch type.
- analytical ultracentrifugation of recombinant APP and sorLA fragments further narrowed down the binding domains to the cluster of complement-type repeats in sorLA that forms a 1:1 stoichiometric complex with the carbohydrate-linked domain of APP
- analysis of involvement of NF-kappaB regulated by capacitative Ca2+ entry in muscarinic receptor-mediated sAPPalpha release enhancement
- family with a later mean age at onset of 50 years (range 48 to 57) and mean age at death of 61 years (range 57 to 68) with a V717L APP mutation.
- The binding of Cu2+ to the copper-binding domain (CuBD) of APP reduces the production of Abeta in cell-culture and animal studies.
- Results suggest that intracellular domains of Notch and amyloid precursor protein are generated by gamma-secretase at the plasma membrane and/or early endosomes.
- memory deficits in middle-aged Tg2576 mice are caused by the extracellular accumulation of a 56-kDa soluble amyloid-beta assembly, which we term Abeta*56 (Abeta star 56)
- In an in vivo transgenic mouse model, mutant APP and Abeta localize to brain mitochondria and are associated with mitochondrial dysfunction and oxidative damage.
- This suggests that distinct mechanisms are responsible for the differential deposition of Abeta in cerebral amyloid angiopathy associated with Alzheimer's disease and that associated with ischemic/cerebrovascular disease.
- analysis of production of amyloid beta-protein and amyloid precursor protein intracellular domain from beta-carboxyl-terminal fragment by gamma-secretase
- results show Down syndrome(DS) brains and trisomic fibroblasts in which APP is not overexpressed, compared to controls, challenging the notion that the widespread amyloid-beta deposits, found in DS individuals, result from an extra copy of APP
- In Abeta amyloid fibrils, Met35 packs against Gly33 in the C-terminus of Abeta40 and against Gly37 in the C-terminus of Abeta42.
- APP mediates cleavage of a receptor tyrosine phosphatase and regulation of beta catenin's trabscriptional activity.
- The compromised activity of MnSOD, a primary antioxidant enzyme protecting mitochondria, may explain mitochondrial dysfunction and provide the missing link between Abeta-induced oxidative stress and Alzheimer's disease.
- The constant and abundant amyloid beta x-42 deposition in sporadic dementia with Lewy bodies suggests that alpha-synucleinopathy is also promoted by amyloid precursor protein dysfunction.
- Amyloid precursor protein (APP) processing can be regulated by caveolin-1 in neuronal cells.
- The present study provides evidence that APP-promoter mutations that significantly increase APP expression levels are associated with AD.
- Plasma Abeta levels representing vascular Abeta deposits years later result in impaired carbon dioxide (CO2)-induced vasomotor reactivity.
- increased neuronal PKCepsilon activity can promote Abeta clearance and reduce AD neuropathology through increased endothelin-converting enzyme activity
- These results suggest that the phosphorylation of APP intracellular domain (AICD) at T668 contributes to the neuronal degeneration in Alzheimer's disease (AD) by regulating its translocation into the nucleus and then affects neurodegeneration.
- Vav activity is required for fAbeta-stimulated intracellular signaling events upstream of reactive oxygen species production and phagosome formation
- Genome-wide study of an F2 intercross between TgCRND8 on an A/J background and C57BL/6 mice, to identify genetic modulators of amyloid accumulation and deposition.
- Studies demonstrate that the full morphological phenotype of IBM including beta-amyloid and tau protein deposits may also develop in children, and that congenital muscle defects may lead to abnormal protein aggregation in IBM-like inclusions.
- A novel mutation (Leu705Val) within the Abeta sequence of a AbetaPP is reported in a family with autosomal dominant, recurrent intracerebral hemorrhages beginning in the sixth decade of life.
- Our study thus provides evidence for a pathogenic mechanism for DS in which increased expression of App, in the context of trisomy, causes abnormal transport of NGF and cholinergic neurodegeneration.
- Deleterious post-translational modifications of APP accumulate in a pathological protein fraction in Alzheimer dissease.
- beta-amyloid peptides are released in association with exosomes
- Amyloid precursor protein (APP) regulates neural stem cell biology in the adult brain, and that altered APP metabolism in Down syndrome or Alzheimer's disease (AD) may have implications for the pathophysiology of these diseases.
- neuroserpin interacts with Abeta(1-42) to form off-pathway non-toxic oligomers and so protects neurons in Alzheimer disease
- The inhibitory role of APP in innervation at the neuromuscular junction and increased expression in inclusion-body myositis suggest that presymptomatic upregulation of APP may be consistent with a potential role for APP in ALS pathology.
- The detection of Abeta11-42 in young DS brain suggests an early role for this N-terminally truncated Abeta peptide in the pathogenesis of SPs in Alzheimer's disease and Down's syndrome.
- Four months of continuous and diversified environmental stimulation resulted in a significant reduction of beta-amyloid (Abeta) plaques and in a lower extent of amyloid angiopathy.
- Incorporation of two N-methyl amino acids into one beta-sheet is sufficient to disrupt that sheet while leaving the other, unmodified beta-sheet intact and able to form fibrils.
- Accumulation of intracellular beta-amyloid protein decreases the activity of important components of the cellular energy generation system, compromises mitochondrial function, and leads to cell death.
- This review focuses on the interactions between amyloid beta peptide (Abeta) and the pan neurotrophin receptor p75NTR and how Abeta-regulated signaling through p75NTR may explain a number of the neurodegenerative characteristics of Alzheimer's disease.
- downstream transcription factors, heat shock factor 1, and DAF-16 regulate opposing disaggregation and aggregation activities to promote cellular survival in response to constitutive toxic Abeta(1-42) aggregation
- APPPS1 mice are well suited for studying therapeutic strategies and the pathomechanism of amyloidosis by cross-breeding to other genetically engineered mouse models.
- APP mRNA splicing can generate isoforms of APP containing a Kunitz protease inhibitor domain (Review)
- quaternary structure of a mature amyloid fibril formed from the Abeta(1-40) peptide; the fibril is polar & represents a left-handed helix consisting of two or three protofilaments; these are organised in a manner so that the cross-section is S-shaped
- measurements of the CuII binding to Abeta16 and Abeta28, models of the soluble Abeta
- ladostigil decreased cell death via inhibition of caspase-3 activation via regulation of the Bcl-2 family proteins and decreased apoptotic-induced levels of holo-APP protein without altering APP mRNA levels, suggesting a posttranscriptional mechanism.
- A subpopulation of dissociated muscle fibers from human betaAPP transgenic mice exhibited a 2-fold increase in resting calcium and membrane depolarization
- Results use data from multidimensional NMR spectroscopy to elucidate the molecular interactions between Abeta peptide and alpha-synuclein which may lead to onset of Lewy body dementia.
- biophysical analysis of conformations of the amyloid-beta (21-30) fragment
- Overexpression of GGA1 increased the APP C-terminal fragment resulting from beta-cleavage but reduced Abeta. GGA1 confined APP to the Golgi, in which fluorescence resonance energy transfer analyses suggest that the proteins come into close proximity.
- LRP binds and endocytoses Abeta42 both directly and via apoE but endocytosed Abeta42 is not completely degraded and accumulates in intraneuronal lysosomes
- DNA condensation is a mechanism of Abeta toxicity: DNA conformation is altered in the presence of Abeta, and Abeta induces DNA condensation in a time-dependent manner
- alphaB-crystallin competes efficiently for Abeta monomer-monomer interactions.
- formation of amyloid fibrils in the plasma protein human serum albumin under different in vitro conditions
- Thus, our present results strongly suggest that AICD triggers apoptosis through the p53-dependent mechanisms.
- We propose that increased AbetaPP is a stressor increasing alphaBC expression in s-IBM muscle fibers. Determining the consequences of alphaBC association with Abeta oligomers could have clinical therapeutic relevance.
- soluble Abeta and tau, but not soluble Abeta alone, have roles in cognitive decline in transgenic mice with plaques and tangle
- These data point to a role of APP intracellular domain in developmental and injury-related cytoskeletal dynamics in the nervous system.
- The load of Abeta aggregates in postmortem brains does not display a significant association with cerebrovascular lesions.
- a fluid lipid monolayer develops immobile domains upon interaction with Abeta aggregates
- The present study provides strong evidence that APP promoter polymorphisms that significantly increase APP expression levels are associated with development of SAD.
- APP significantly modulates Ca(2+) store depletion-induced cell death in a store-operated channel- and CHOP-dependent manner, but independent of the unfolded protein response.
- APP has the potential to activate aberrant neuronal cell cycle re-entry in Alzheimer's disease. [review]
- In the E22Q/D23N, D23N/K28Q, and E22Q/D23N/K28Q mutants, hydration becomes much less significant because the mutated residues have neutral amide side-chains.
- in the cortex and hippocampus of transgenic mice expressing mutant type of APP, the mRNA of some endoplasmic reticulum chaperones was up-regulated in comparison with wild-type mice
- These data suggest mechanistic similarities in the nucleation behaviour of different amyloid-like fibrils and aggregates.
- Class 1 antigens undergo extra-cellular domain cleavage mediated by alpha-secretases and the cleavage product is subsequently cleaved by PS1/gamma-secretase.
- Amyloid-beta (Abeta) peptide fragment 1-42 increases neuronal pentraxin 1 expression before inducing apoptotic death of cortical neurons, indicating that Abeta contributes to the pathology of Alzheimer's disease.
- Cleavage of amyloid precursor protein (APP)may play a critical role in the development of synaptic and behavioral dysfunction in APP transgenic mice.
- alkalizing drugs induce the accumulation of amyloid precursor protein intracellular domain, a mechanism likely mediated by the endosome/lysosome pathway
- Abeta induced integrin focal adhesion signaling pathways that mediate cell cycle activation and cell death in Alzheimer's disease [REVIEW]
- provides comprehensive profile of non-cognitive behaviors of APP/PS1 transgenic mouse model; reveals behavior impairments that may be pertinent to behavior seen in AD patients
- demonstrates a spatial learning deficit in 7-month-old APP(Swe) + PSEN1DeltaE9 bigenic mice using an adaptation of the Barnes maze
- Abeta40 has anti-amyloidogenic effect in vivo.
- beta-amyloid (Abeta) induces the proapoptotic protein Bcl-2 interacting mediator of cell death (Bim) in cultured hippocampal and cortical neurons.
- Lipid membranes may be involved in templating the pathological misfolding of amyloid beta protein.
- analysis of amyloid protofilaments alignment by linear dichroism
- reduced presenilin proteolytic function leads to increased Abeta42/Abeta40 in Alzheimer disease (Review)
- BACE1 and BACE2 may act as alternative alpha-secretase-like proteases in proteolytic processing of IL-1R2 and APP
- study shows subunit mu1B of AP-1B binds to the cytoplasmic tail of APP in a Tyr653-dependent way; model proposed for polarized targeting of APP in which sorting of APP to basolateral domain depends on binding of AP-1B on Tyr653 in basolateral endosomes
- While the N-terminal residues 1-16 may not play a major role in neurotoxicity and aggregation, a lack of N-terminal fragment Abeta peptide does not display the neurotoxicity of either full-length or 17-21, 25-35 truncated Abeta peptides
- GxxxG motifs within the amyloid precursor protein transmembrane sequence are critical for the etiology of Abeta42.
- APP could be acting through a semaphorin receptor as well
- Results show significant decreases of Abeta1-42 in Alzheimer disease, and Abeta1-38 in frontotemporal dementias. A novel peptide (probably an oxidized alpha-helical form of Abeta1-40) was significantly increased in Lewy body dementia.
- Neuronal expression of human amyloid precursor protein/Abeta is sufficient to reduce Reelin expression in a specific population of entorhinal cortical pyramidal neurons in vivo.
- Physiological concentrations of naturally secreted Abeta dimers and trimers, but not monomers, induce progressive loss of rat hippocampal synapses in vitro.
- Notch1 intracellular domain plays the role of a negative regulator in AICD signaling via the disruption of the AICD-Fe65-Tip60 trimeric complex.
- altered phosphorylation state of eIF2alpha evoked by Abeta may account for the decreased efficacy of mRNA translation and de novo protein synthesis required for synaptic plasticity
- high-density platelets undergo activation likely by increased frequency of platelet-platelet collisions, which determines the activation of APP beta-processing with consequent release of Abeta(40)
- protein phosphorylation has a role in APP sorting under stress conditions
- APLP2 and APP have roles in sperm function
- APP and PS1 are closely associated in the centrosomes of the H4 cell
- Data show that endogenous beta-amyloid precursor protein and amyloid beta peptide immunoreactivities colocalize with microtubules in interphase cells.
- results suggest that common variation in the APP gene is not a significant risk factor for late-onset Alzheimer's disease
- Increase in APP gene dosage is linked to a phenotype consisting of early onset dementia and CAA with frequent ICH. The phenotype does not depend on the size of the duplicated region, but may vary between families and between the genders.
- time resolved static light scattering was applied to investigate the size and shape of growing beta-amyloid aggregates preceding plaque formation
- findings show that the Arctic mutation favors proamyloidogenic APP processing by increased beta-secretase cleavage, as demonstrated by altered levels of N- and C-terminal APP fragments
- multivesicular bodies are essential organelles for APP metabolism and all APP metabolites can be secreted in the extracellular space
- Results suggest that amyloid beta40 plays a critical, protective role in Alzheimer's by inhibiting the aggregation of amyloid beta42 monomer.
- We found that levels of mRNAs expressing mitochondrial COX subunits decreased significantly in Amyloid-beta-treated SK-N-SH cells in a dose-dependent manner
- Abeta activates the apoptosis signal-regulating kinase 1 (ASK1)-p38MAP kinase-p53-Bax cascade to cause cerebral endothelial cell death in a protein phosphatase 2A (PP2A)-dependent manner.
- Here, we show that long-term systemic administration of anti-APP beta-site antibodies to Tg2576 transgenic mice improved mouse cognitive functions associated with a reduction in both brain inflammation and the incidence of microhemorrhage.
- Heparin binding domains on the proteins have been utilised to develop a one-step fast-performance-liquid-chromatography (FPLC) purification of sAPPs from the conditioned media.
- an anti-A beta 1-11 antibody binds to different beta-amyloid species, inhibits fibril formation, and disaggregates preformed fibrils but not the most toxic oligomers
- a specific nonfibrillar Abeta assembly Abeta*56 is a likelier determinant of functional deficits in hAPP mice than fibrillar Abeta deposits
- aggressive presenilin-1 mutations cause insensitivity to Abeta42-lowering nonsteroidal anti-inflammatory drugs and gamma-secretase inhibitors
- Two mutants of PrP, PG14 and A116V, that are associated with familial human prion diseases failed to inhibit the beta-secretase cleavage of APP
- The ratio of soluble APPalpha-KPI protein levels to total APP protein increased in AD, and also correlated with GFAP protein levels in AD.
- The data show that Abeta oligomer formation is inhibited by promoting fibril formation, which suggests that the relative pathological significance of oligomers and fibrils may be tested in vivo using methylene blue.
- This study suggests a possible role for APP in normal cognitive ageing, in addition to its role in Alzheimer's disease
- Rab5 activation via amyloid precursor protein signal pathway mediates neuronal apoptosis.
- These results suggest that the neurotrophic effect of platelet-derived growth factor is mediated in part via upregulation of the expression and release of secreted amyloid precursor protein alpha.
- Findings suggest different effects of wild-type and mutant hAPP on neuronal connectivity.
- Distinct pathways of APP phosphorylation operate in proliferating, differentiating, stressed, and degenerating neurons.
- Determination and assignment of the redox potentials clarify some misconceptions in the redox reactions involving Abeta and provide new insight into the possible roles of redox metal ions in the Alzheimer's disease (AD) pathogenesis.
- Fe65 can control luciferase activity without stabilizing the labile APP intracellular domain fragment.
- Role for the transcription factor AP-2alpha in the regulation of APP gene expression in human keratinocytes.
- Stable insertion of ABETA peptide into the ER membrane strongly correlates with its length.
- Decreased insulin receptor signaling promotes the autophagic degradation of beta-amyloid peptide in C. elegans.
- HtrA2 has a role as a regulator of APP metabolism through endoplasmic reticulum-associated degradation
- DNA prime-adenovirus boost regimen can enhance Th2-biased responses with adenovirus vector encoding 11 tandem repeats of amyloid beta 1-6 in mice.
- In a model system of cultured mouse neurons, the deeper layer neurons are more resistant to toxic effects of Abeta than are cells from the more superficial strata, suggesting that an underlying biology drives the Alzheimer's progression pattern.
- Soluble circulating LRP (sLRP) provides key endogenous peripheral 'sink' activity for amyloid beta in humans.
- Data demonstrate severe amyloid deposition in mammary glands of familial amyloid polyneuropathy patients.
- Hypericum perforatum extract and its single compounds affect amyloid-beta mediated toxicity in microglial cells
- downregulation of myosin II-B, the major myosin isoform in neurons, is able to increase Abeta deposition, concomitantly altering the subcellular localization of APP
- The chronic blockade of IL-1 signalling in the brain was associated with an atrophic phenotype of the brain, and with modified levels of APP and PS1.
- results indicate that Abeta peptide increases MMP-9 secretion through integrins; MMP-9 then directly processes cell surface APP695 with an alpha-secretase like activity, substantially reducing the levels of secreted Abeta peptide
- after addition of Abeta, platelet number, platelet mitochondrial membrane potential and ATP content were lowered while no protective effects of estradiol benzoate and genistein had been observed.
- prostaglandin E(2) (PGE(2)), a strong inducer of inflammation, stimulates the production of Abeta in cultured human embryonic kidney (HEK) 293 or human neuroblastoma (SH-SY5Y) cells, both of which express a mutant type of APP
- Aberrant increases in network excitability and compensatory inhibitory mechanisms in the hippocampus may contribute to Abeta-induced neurological deficits in hAPP mice and, possibly, also in humans with AD.
- physiologically relevant levels of naturally secreted Abeta interfere with insulin receptor function in hippocampal neurons and prevent the rapid activation of specific kinases required for long term potentiation
- Fe65 regulation of APP proteolysis may be integrally associated with its nuclear signaling function, as all antecedent proteolytic steps prior to release of Fe65 from the membrane are fostered by the APP-Fe65 interaction
- Tyr687 appears to be a critical residue determining APP targeting and processing via different pathways, including endocytosis and retrograde transport
- Abeta42 and Abeta40 act as potent opsonins for LDL, E-LDL and Ox-LDL and enhance cellular cholesterol accumulation as well as Abeta-deposition in vessel wall macrophages
- the luminal juxtamembrane region of APP is an important regulatory domain that modulates gamma-secretase-dependent intramembrane proteolysis, particularly in differentiating gamma- and epsilon-cleavages
- All salts examined promote aggregation strongly.In the presence of salts, fibrils are associated with smaller diameters, narrower crossover distances and lower amide I maxima
- This structural study describes the mechanism of interaction between divalent copper ions and amyloid beta precursor protein (Abeta) that leads to a decrease in Abeta production and to alleviation of symptoms of Alzheimer disease in mouse models.
- although the use of a specific gene influences the tissue distribution of amyloid, each light chain exhibits one or more determinants of organ-specificity, which originate from somatic mutations and post-translational modifications
- The increasing levels of Abeta in CSF during early childhood of Down syndrome patients observed in this study are probably due to the trisomy of the Abeta precursor APP, which leads to an overproduction of Abeta.
- HLA-B27 has a role in Beta 2-microglobulin amyloid deposit, as shown in transgenic rats
- His6, His13, and His14 residues of Abeta1-42 control the redox activity of transition metals present in senile plaques.
- The Alzheimer's disease-associated amino acid substitutions at Glu-22 or Asp-23 destabilized the turn and the magnitude of the destabilization is correlated with oligomerization propensity.
- The activation of muscarinic acetylcholine receptors, PKC and MAP kinase is involved in Hup A-induced alphaAPPs secretion in neuroblastoma cells and suggest multiple pharmacological mechanisms of Hup A regarding the treatment of Alzheimer's disease (AD).
- Data show that CSF levels of beta-amyloid(1-42) are not significantly different between the brain tumor patients and non-tumor patients.
- These data implicate Mint3 activity as a critical determinant of post-Golgi APP traffic.
- Abeta 1-42 induces mild endoplasmic reticulum stress in an aggregation state-dependent manner.
- Our data indicate that different signalling pathways are involved in retinoic acid-induced up-regulation of the secretases.
- Abeta-induced and mitochondria-dependent cytotoxic pathways might play an important role in Alzheimer's disease pathogenesis.
- Exclusion of the native alpha-helix from the amyloid fibrils of a mixerd alpha/beta protein.
- Using transgenic mice expressing human cystatin C (encoded by CST3), study shows that cystatin C binds soluble amyloid-beta peptide and inhibits cerebral amyloid deposition in amyloid-beta precursor protein (APP) transgenic mice.
- Study shows that overexpression of human cystatin C in brains of APP-transgenic mice reduces cerebral amyloid-beta deposition and that cystatin C binds amyloid-beta and inhibits its fibril formation.
- Direct titrations of HSA with Abeta40 was monitored using circular dichroism spectroscopy and a dissociation constant (K(d)) of 5+/-1 microM for a HSA complex with Abeta40 was obtained.
- analysis of protofibril assemblies of the arctic, Dutch, and Flemish mutants of the Alzheimer's Abeta1-40 peptide
- Beta-amyloid precursor protein (APP) and CCL2 chemokine synergistically enhance aggregated APP clearance by 3 different pathways in mononuclear phagocytes derived from transgenic mouse models of Alzheimer's disease.
- Duplication of the APP gene is not a common cause of Alzheimer's disease with cerebral angiopathy in Swedish and Finnish populations.
- This review focuses on the highly regulated process underlying intracellular trafficking of beta-amyloid peptides (Abeta), the disturbance of which directly impacts Abeta production and its critical role in the pathogenesis of Alzheimer's disease.
- LRP-1/LDLR-mediated uptake of A beta results in degeneration of perivascular cells.
- Fyn, due in part to its effects on Dab1, regulates the phosphorylation, trafficking, and processing of APP and apoEr2.
- These results illustrate the regulatory mechanisms by which AICD transcriptional activity might be regulated via covalent conjugation with Nedd8.
- Amyloid assembly may involve fluctuation between a fast-growing and a blocked state in which the fibril is kinetically trapped because of intrinsic structural feature
- In fetal brain, protein expression levels of APP was comparable between DS and controls. But APP was significantly increased in adult brain.
- Membrane fusogenic activity of the Alzheimer's peptide A beta (1-42) demonstrated by small-angle neutron scattering.
- amyloid precursor protein (APP) ectodomain homophilic interactions are regulated by the loop region and affect beta-secretase cleavage of APP
- Motor strength was considerably reduced in APP transgenic mice. Neurological impairments showed by APP mice had an early onset and worsened with progressive aging, in parallel to gradual accumulation of Abeta in brain.
- The atypical clinical phenotype with long prodromal phase, autonomic failure and seizures in this new proband with the APP Thr714Ala mutation illustrates the clinical heterogeneity in families with identical pathogenic mutations.
- Cellular localization of Nicastrin affects amyloid beta species production.
- Amyloidogenic processing but not amyloid precursor protein (APP) intracellular C-terminal domain production requires a precisely oriented APP dimer assembled by transmembrane GXXXG motifs.
- Comparing the beta2-m fragment with Abeta indicates that while both adopt similar beta-strand-turn-beta-strand motifs, the final amyloid structures can be dramatically different .
- Synthetically prepared Abeta(1-42) specifically suppresses spontaneous synaptic activity resulting from a reduction of vesicular release at terminals of both gamma-aminobutyric acid GABAergic and glutamatergic synapses.
- This study reiterates DL-alpha-lipoic acid as a potent free radical scavenger to combat oxidative vulnerability in the treatment for amyloid beta (25-35) toxicity.
- The dissociation constants are correlated to both the Abeta42/Abeta40 ratio and the mean age of disease onset in AD patients.
- analysis of the minimal copper- and zinc-binding site sequence in amyloid-beta peptides
- Intracellular copper deficiency increases amyloid-beta secretion by diverse mechanisms.
- wild-type or Swedish mutated betaAPP overexpression modulates BACE1 promoter transactivation and activity via an NFkappaB-dependent pathway.
- SNX17 regulates amyloid precursor protein trafficking and processing in the early endosomes
- The lowest values of beta amyloid were found in Alzheimer's disease subjects in moderate to severe stages of disease.
- Findings indicate Amyloid beta protein is associated with cognitive function, body fat and physical fitness in neurologically healthy older adults
- Results describe the effect of high cholesterol incorporated into human neuroblastoma cells in Abeta-mediated neurotoxicity and the role of reactive oxygen species (ROS) generation.
- The effects of (1-40)betaA and (25-35)betaA peptides on human amylin (hA)-mediated cell death and [(125)I-Tyr(37)]hA precipitation, was investigated.
- A novel amyloid protein precursor mutation (Glu693Delta)-producing variant in Japanese pedigrees has been suggested as a cause of Alzheimer's-type dementia because of enhanced formation of synaptotoxic amyloid beta oligomers rather than amyloid fibrils.
- compare the pathogenicity of human Abeta42 mutants with differing tendencies to aggregate in the Drosophila brain
- Promotion of amyloid beta protein misfolding and fibrillogenesis by a lipid oxidation product.
- The amyloid beta peptide pattern in cerebrospinal fluid is able to predict Alzheimer's disease in patients with mild cognitive impairment with a sensitivity of 91% and specificity of 64%.
- We are the first to demonstrate the distribution of Abeta in human platelets and that Abeta activation of platelets is mediated, at least partially, by the PLCgamma2-PKC pathway, and Abeta triggers thrombus formation in vivo.
- Data show that a presenilin-1 280Glu-->Ala mutation alters C-terminal amyloid precursor protein processing, yielding longer amyloid beta peptides, and discuss the implications for Alzheimer's disease.
- Data show that the E280A mutation in presenilin 1 is not associated with increased production of amyloid-beta in non-neuronal peripheral tissues, which is in contrast to the expectation in a gamma-secretase gain of function.
- Review gives further evidence for a pivotal role of intraneuronal Abeta accumulation as a main pathological trigger in transgenic mouse models of Alzheimer's disease.
- In this review, Abeta oligomers induce a reduction of postsynaptic density protein 95 (PSD-95) and NMDA glutamate receptors in cultured rat hippocampal neurons.
- In a model of Alzheimer's disease, mitochondrial dysfunction is exacerbated by the presence of soluble Abeta species from transgenic mice as a very early event during pathogenesis.
- Recent studies in this review suggest that pathological alterations of APP processing in Alzheimer's disease may prevent neuronal differentiation of human neural progenitor cells.
- co-occurrence of pathology typical of sCJD & AD & inverse association between Abeta & PrP(Sc) in a subgroup of sCJD patients is indicative of common pathways involved in generation or clearance of Abeta & PrP(Sc) in a subgroup of sCJD patients
- Abeta-peptide in its homogeneous globular A beta-oligomer (Abeta-globulomer) conformation is a structural entity which is independent from amyloid fibril formation.
- identifies SNX33 as a new endocytic protein, which modulates amyloid precursor protein endocytosis and APP alpha-secretase cleavage, and demonstrates that the rate of APP endocytosis is a major control factor for APP alpha-secretase cleavage
- The posterior cingulate is preferentially vulnerable to both effects of transgene in the PDAPP mouse, and both are independent of amyloid deposition.
- The last 37 residues of LRP cytoplasmic tail (LRP-C37) lacking the NPxY motifs and FE65 binding mediate the core pro-amyloidogenic activity of soluble cytoplasmic tail of LRP (LRP-ST).
- BACE and APP come into close proximity within the cell, but probably not on the cell surface.
- The tendency for a higher prevalence of headaches held for different PSEN1 and APP mutations but was not significant unless all families were combined.
- Transglutaminase induces protofibril-like amyloid beta-protein assemblies that are protease-resistant and inhibit long-term potentiation
- the altered calcium signaling of APPswe transgenic neurons was unlikely to be due to modulation of the NMDA or nicotinic neurotransmitter systems, and did not depend on secreted APP derivates
- TMP21 behaves as a regulator of gamma- but not epsilon-cleavages of beta-amyloid precursor protein generated by presenilin-dependent gamma-secretase complex.
- The E22Q mutation increases aggregation rates of the 15-28 fragment by lowering the barrier for Abeta monomer deposition onto a fibril.
- the catalytic domain of insulin-degrading enzyme forms a denaturant-resistant complex with amyloid beta peptide
- Affected and nonaffected carriers of the Arctic APP mutation from the Swedish and American families were investigated clinically.
- Positron emission tomography with 11C-PiB and magnetic resonance imaging were performed for 2 patients, 49-year-old and 60-year-old siblings with APP locus duplication, with hereditary Alzheimer disease and cerebral amyloid angiopathy.
- These results suggest that HS codeposits with Abeta40 in neuritic plaques and is mainly derived from glial cells.
- beta-sheet architecture underlies in vitro and in vivo beta2-microglobulin amyloid fibrils
- Abeta42 and Abeta38 species can be independently generated by gamma-secretase and there is probably not a precursor-product relationship between these peptides
- ER stress-induced homocysteine toxicity may play an important physiological role in enhancing the pathogenesis of Abeta-induced neuronal degeneration
- I213T mutant presenilin-1/gamma-secretase in cell models and knock-in mouse brains: familial Alzheimer disease-linked mutation impairs gamma-site cleavage of amyloid precursor protein C-terminal fragment beta
- GM-CSF operates downstream of CD40/CD40L interaction and that GM-CSF modulates Abeta production by influencing APP trafficking
- PSEN1 and APP gene mutations may not be uncommon in Korean patients with early-onset Alzheimer's disease
- the expressions of Swedish double mutation of amyloid precursor protein (Swe-APP)increased mRNA and protein levels of cyclin D1 and cyclin B1
- the alpha-helical membrane-bound human islet amyloid polypeptide has a role in membrane-mediated misfolding
- CD147 expression influences Abeta levels by an indirect mechanism involving MMPs that can degrade extracellular Abeta.
- rodent and human Abeta are effective in modulating K currents
- Abeta and tau pathology are consistent with a model in which both synaptic loss and dysfunction are linked to a synaptic amyloid cascade within the synaptic compartment.
- APP-regulated FE65 plays an important role in the early stress response of cells and that FE65 deregulated from APP induces apoptosis.
- A three-dimensional structure of a mature amyloid fibril formed by Abeta(1-40) peptide, determined by electron cryomicroscopy at approximately 8-A resolution, was presented.
- Data suggest a possible role for APP and/or amyloid-beta in the development of obesity-related insulin resistance and adipose tissue inflammation.
- The results of this study demonstrate that the D664A mutation either completely precludes, or markedly delays (beyond 13 mo) the appearance of AD-like deficits in this mouse model of AD.
- Abeta pathology is regulated by beclin 1 through a pathway that involves autophagy
- beclin 1 deficiency disrupts neuronal autophagy, modulates APP metabolism, and promotes neurodegeneration
- Beta-amyloid peptide stimulates endozepine release from rat astrocytes through an N-formyl peptide receptor positively coupled to protein kinase A and protein kinase C.
- This is the first report, evidencing the presence of changes in eating and drinking behavior in a single transgenic Alzheimer mouse model.
- Our findings indicate that hippocampal and DLS dendritic spines in hAPPswe mutants undergo a different pattern of morphological changes over time and point to minor alterations in the microanatomy of DLS spines.
- These studies suggest that glioma and glioblastoma exhibit robust upregulation of proinflammatory and neurodegenerative genetic markers beta-amyloid precursor protein.
- familial Alzheimer's disease mutations in the polypeptide backbone of APP can affect processing of the attached N-glycans; however, whether these changes in N-glycosylation affect Abeta production remains to be established
- combinations of the cube copying test with MMSE, rCBF and CSF A beta (42) measurements can identify subgroups of MCI subjects with either substantially reduced or increased risk for future development of Alzheimer's disease
- In patients with Alzheimer disease, low plasma levels of Abeta40 and Abeta42 are associated with a significantly more rapid cognitive decline than are high levels in patients with Alzheimer disease, using the Blessed Dementia Scale.
- Data show that Alzheimer's disease patients have ower Abeta1-42 levels.
- An increase in APP intracellular domain generation does not directly promote gene activation of previously proposed target genes.
- Amyloid-beta protein dimers impair synaptic plasticity and memory
- APPs-alpha regulates the function of APP in neurite outgrowth via the novel mechanism of competing with the binding of APP to Itgbeta1
- amyloid-beta rise and gamma-secretase inhibitor potency depend on the level of substrate expression
- Abeta was found to be associated with plasma lipoproteins, especially those enriched with triglyceride; Abeta may be increased in normolipidaemic Alzheimer's disease subjects, commensurate with possible disturbances in postprandial lipoprotein homeostasi
- Study determined that the CALHM1 P86L polymorphism is associated with Alzheimer's disease, further found that the P86L polymorphism increases abeta levels by interfering with CALHM1-mediated Ca(2+) permeability.
- Data show that increased Abeta42 levels and an elevated Abeta42/Abeta40 ratio in neurons from sporadic as well as from familial cases of Alzheimer's disease, whereas Abeta40 levels remain unchanged between the cases and controls.
- the 24-28 bend motif is retained in all E22 mutants, suggesting that mutations involving residue E22 may not affect the structure of the folding nucleation site of Abeta
- Numb endocytic adapter proteins regulate the transport and processing of the amyloid precursor protein in an isoform-dependent manner and have roles in Alzheimer disease pathogenesis
- structure of the high-affinity Cu(2+) binding site is consistent with the hypothesis that the redox activity of the metal ion bound to Abeta can lead to the formation of dityrosine-linked dimers found in AD
- Hence, the experimental model demonstrates that a prion infection of the CNS promotes selectively formation of FA-extractable Abeta(1-42) in Tg2576 mice.
- Lysines 587 and 595 of APP, which are immediately adjacent to the site of beta-secretase cleavage, are covalently modified by SUMO proteins in vivo.
- simultaneous presence of human mutated Tau(VLW) and plaque-amyloid (and/or APP(SW)) potentiates and anticipates tau phosphorylation at the 12E8 epitope, intensifying pyramidal neuron immunostaining and tau filament formation in this alzheimer's model
- APP may serve as a cellular cholesterol sensor that is linked to mechanisms for suppressing cellular cholesterol uptake.
- The intracellular domain of amyloid precursor protein can induce neuron-specific apoptosis.
- study found strong positive correlation between changes in brain interstitial fluid Abeta concentrations & neurological status of acute brain injury patients, with Abeta increasing as neurological status improved & falling as neurological status declined
- The central core sequence of Abeta peptide associated with Alzheimer's disease, Abeta(16-22), is developed as an experimental system in order to evaluate amino acid cross-strand pairing interactions in protein beta-structural assembly and stability.
- The age-related elevation of oxidative damage was observed in human mutant APP mice brain compared to that of wild-type mice brain.
- APPrearranges to form a micelle-bound structure with alpha-helical segments with additions of SDS or lithium dodecyl sulfate
- Beta-amyloid may contribute selectively to cognitive impairment of Lewy body disease and may contribute to timing of dementia relative to motor signs of parkinsonism.
- polyphenols have an effect on amyloid beta-protein self-assembly and cytotoxicity
- analysis of how sulfated polysaccharides promote the assembly of amyloid beta(1-42) peptide into stable fibrils of reduced cytotoxicity
- Study determined the crystal structure of the carboxy-terminal APP intracellular domain in complex with the C-terminal phosphotyrosine-binding (PTB) domain of Fe65; The unique interface involves the NPxY PTB-binding motif and two alpha helices.
- study demonstrated that Abeta(1-40), levels of sCD40 and sCD40L are increased in Alzheimer's disease and declining MMSE scores correlated with increasing sCD40L, which in turn, correlated positively with Abeta(1-42)
- Data show that the pathological deposits with antibodies against amyloid-beta protein has involved in the neuropathogenesis of the amyotrophic lateral sclerosis/parkinsonism-dementia complex of Guam.
- thioflavin T and its neutral analog BTA-1 bind to protofibrils of the Alzheimer's disease Abeta(16-22) peptide
- These results suggest that phosphorylation of APP at Tyr687 regulates APP processing by alpha- and gamma-secretases, determining the expression level of APP intracellular domain.
- Dexras1 functions as a suppressor of FE65-APP-mediated transcription, and FE65 tyrosine 547 phosphorylation enhances FE65-APP-mediated transcription, at least in part, by modulating the interaction between FE65 and Dexras1
- Microdomain switching is a mechanism of cholesterol- and activity-dependent regulation of APP processing in neurons.
- rapid LRP1-dependent internalization of A beta occurs under the blood-brain barrier-specific cellular context
- Data show that valproic acid decreased amyloid beta production by inhibiting GSK-3beta-mediated gamma-secretase cleavage of amyloid protein precursor both in vitro and in vivo.
- Data show a significant positive correlation between beta-amyloid burden and progranulin in the medial temporal lobe in dementia with Lewy bodies.
- analysis of amyloid beta peptide hydrolyzing activity of nonphysiological immunoglobulin variable domain scaffolds
- Data show that transient intraneuronal A beta correlates with neuron loss in the frontal cortex of APP/PS1KI mice.
- p120 catenin is a unique positive regulator of the gamma-secretase processing of cadherins and a negative regulator of the amyloid precursor protein processing
- study describes a full structural model for amyloid fibrils formed by the 40-residue beta-amyloid peptide associated with Alzheimer's disease (Abeta(1-40)), based on numerous constraints from solid state NMR and electron microscopy
- S-palmitoylation plays a role in stability and raft localization of nicastrin and APH-1, but does not directly modulate gamma-secretase processing of APP and other substrates.
- APP, through amyloid beta production, causes an imbalance of mitochondrial fission/fusion that results in mitochondrial fragmentation and abnormal distribution, which contributes to mitochondrial and neuronal dysfunction
- chromatin immunoprecipitation analysis also reveals AICD binding to the neprilysin promoter in rat primary neurons but not in HUVEC cells
- The amyloid-beta protein precursor/ nitric oxide synthase 2 inducible bigenic mice progress from production and amyloid deposition to hyperphosphorylated normal mouse tau at Alzheimer's disease associated epitopes--REVIEW
- APP gene polymorphisms at codon 718 (I>L), 720 (L>S), and 710 (V>G) can be found in certain Chinese/Taiwanese patients with Alzheimer's disease.
- These data demonstrate that a specific oligomeric Abeta(1-42) aggregation species can potently initiate the THP-1 monocyte maturation process.
- in mice overexpressing wild-type human APP we found an early memory impairment, particularly in the water maze and to a lesser extent in the object recognition task, but beta-amyloid peptide was barely detectable in the hippocampus
- These data suggest that DNM2 expression is reduced in late-onset Alzheimer's disease , which results in the accumulation of APP in lipid raft-rich plasma membranes.
- in conclusion, in patients with Alzheimer disease, macrophages appear to shuttle Abeta from neurons to vessels where their apoptosis may release fibrillar Abeta, contributing to cerebral amyloid angiopathy
- Sequence deletion and Abeta oligomers produced exhibit toxicity in the extracellular space and within the cells themselves
- study concludes that Abeta can modulate the cellular expression of agrin and glypican-1, which may contribute to the accumulation of these heparan sulfate proteoglycans in Alzheimer's disease lesions
- findings show JNK plays a key role in phosphorylation of APP-T668 in a model of Alzheimer's disease; results suggest important link between APP metabolism & the JNK pathway & contribute to shed light on the molecular signalling pathway of this disease
- These results suggest that IGF-1 promotes Abeta production through a secretase-independent mechanism involving APP phosphorylation.
- O-mannosylation is required for the solubilization of exogenously expressed human APP.
- Amino acid substitution in ABPP inhibits parenchymal amyloidosis but exacerbates vascular amyloid, explaining the destribution of amyloid in amyloidosis.
- These data show that senile plaques are a potential reservoir of oligomeric Abeta, which colocalizes with the postsynaptic density and is associated with spine collapse.
- human APP gene plays role in synaptogenesis in transgenic lines of Drosophila melanogaster whose nerve cells express the human APP695 isoform, truncated APPs, and the presynaptic marker synaptotagmin driving the sequence of the green fluorescent protein.