APP

Summary

Gene Symbol: APP
Description: amyloid beta precursor protein
Alias: AAA, ABETA, ABPP, AD1, APPI, CTFgamma, CVAP, PN-II, PN2, preA4, amyloid-beta A4 protein, alzheimer disease amyloid protein, amyloid beta (A4) precursor protein, amyloid beta A4 protein, amyloid precursor protein, beta-amyloid peptide, beta-amyloid peptide(1-40), beta-amyloid peptide(1-42), beta-amyloid precursor protein, cerebral vascular amyloid peptide, peptidase nexin-II, protease nexin-II, testicular tissue protein Li 2
Species: human
Products:     APP

Top Publications

  1. Muresan Z, Muresan V. The amyloid-beta precursor protein is phosphorylated via distinct pathways during differentiation, mitosis, stress, and degeneration. Mol Biol Cell. 2007;18:3835-44 pubmed
    Phosphorylation of amyloid-beta precursor protein (APP) at Thr(668) is a normal process linked to neurite extension and anterograde transport of vesicular cargo...
  2. Granic A, Padmanabhan J, Norden M, Potter H. Alzheimer Abeta peptide induces chromosome mis-segregation and aneuploidy, including trisomy 21: requirement for tau and APP. Mol Biol Cell. 2010;21:511-20 pubmed publisher
    ..mechanism underlying mosaic chromosome aneuploidy in AD and report that FAD mutations in the Alzheimer Amyloid Precursor Protein gene, APP, induce chromosome mis-segregation and aneuploidy in transgenic mice and in transfected cells...
  3. Guerreiro R, Baquero M, Blesa R, Boada M, Brás J, Bullido M, et al. Genetic screening of Alzheimer's disease genes in Iberian and African samples yields novel mutations in presenilins and APP. Neurobiol Aging. 2010;31:725-31 pubmed publisher
    Mutations in three genes (PSEN1, PSEN2, and APP) have been identified in patients with early-onset (<65 years) Alzheimer's disease (AD)...
  4. Lee H, Kumar P, Fu Q, Rosen K, Querfurth H. The insulin/Akt signaling pathway is targeted by intracellular beta-amyloid. Mol Biol Cell. 2009;20:1533-44 pubmed publisher
    Intraneuronal beta-amyloid (Abeta(i)) accumulates early in Alzheimer's disease (AD) and inclusion body myositis...
  5. Cheng N, Cai H, Belluscio L. In vivo olfactory model of APP-induced neurodegeneration reveals a reversible cell-autonomous function. J Neurosci. 2011;31:13699-704 pubmed publisher
    b>Amyloid precursor protein (APP) has long been linked to the neurodegeneration of Alzheimer's disease (AD), but the associated cell death has been difficult to capture in vivo, and the role of APP in effecting neuron loss is still unclear...
  6. Kienlen Campard P, Tasiaux B, Van Hees J, Li M, Huysseune S, Sato T, et al. Amyloidogenic processing but not amyloid precursor protein (APP) intracellular C-terminal domain production requires a precisely oriented APP dimer assembled by transmembrane GXXXG motifs. J Biol Chem. 2008;283:7733-44 pubmed publisher
    ..Abeta is produced by the sequential cleavage of the amyloid precursor protein (APP) by beta- and gamma-secretases...
  7. Müller T, Concannon C, Ward M, Walsh C, Tirniceriu A, Tribl F, et al. Modulation of gene expression and cytoskeletal dynamics by the amyloid precursor protein intracellular domain (AICD). Mol Biol Cell. 2007;18:201-10 pubmed
    Amyloidogenic processing of the amyloid precursor protein (APP) results in the generation of beta-amyloid, the main constituent of Alzheimer plaques, and the APP intracellular domain (AICD)...
  8. Michaki V, Guix F, Vennekens K, Munck S, Dingwall C, Davis J, et al. Down-regulation of the ATP-binding cassette transporter 2 (Abca2) reduces amyloid-? production by altering Nicastrin maturation and intracellular localization. J Biol Chem. 2012;287:1100-11 pubmed publisher
    ..Reduced Abca2 levels in mammalian cells in vitro, in Drosophila melanogaster and in mice resulted in altered ?-secretase processing of APP, and thus A? generation, without affecting Notch cleavage.
  9. Cruchaga C, Haller G, Chakraverty S, Mayo K, Vallania F, Mitra R, et al. Rare variants in APP, PSEN1 and PSEN2 increase risk for AD in late-onset Alzheimer's disease families. PLoS ONE. 2012;7:e31039 pubmed publisher
    Pathogenic mutations in APP, PSEN1, PSEN2, MAPT and GRN have previously been linked to familial early onset forms of dementia...

More Information

Publications494 found, 100 shown here

  1. Burgos P, Mardones G, Rojas A, daSilva L, Prabhu Y, Hurley J, et al. Sorting of the Alzheimer's disease amyloid precursor protein mediated by the AP-4 complex. Dev Cell. 2010;18:425-36 pubmed publisher
    ..we report the interaction of an YKFFE sequence from the cytosolic tail of the Alzheimer's disease amyloid precursor protein (APP) with the mu4 subunit of AP-4...
  2. Millucci L, Ghezzi L, Bernardini G, Santucci A. Conformations and biological activities of amyloid beta peptide 25-35. Curr Protein Pept Sci. 2010;11:54-67 pubmed
    Amyloid-beta (Abeta) peptide is commonly found in human Alzheimer's disease (AD) brain and is the main component of Alzheimer amyloid plaques...
  3. De Chiara G, Marcocci M, Civitelli L, Argnani R, Piacentini R, Ripoli C, et al. APP processing induced by herpes simplex virus type 1 (HSV-1) yields several APP fragments in human and rat neuronal cells. PLoS ONE. 2010;5:e13989 pubmed publisher
    ..neurotoxic peptides, which occurs during amyloidogenic endoproteolytic processing of the transmembrane amyloid precursor protein (APP)...
  4. Kim T, Vidal G, Djurisic M, William C, Birnbaum M, Garcia K, et al. Human LilrB2 is a ?-amyloid receptor and its murine homolog PirB regulates synaptic plasticity in an Alzheimer's model. Science. 2013;341:1399-404 pubmed publisher
    ..These findings imply that LilrB2 contributes to human AD neuropathology and suggest therapeutic uses of blocking LilrB2 function. ..
  5. Zempel H, Luedtke J, Kumar Y, Biernat J, Dawson H, Mandelkow E, et al. Amyloid-β oligomers induce synaptic damage via Tau-dependent microtubule severing by TTLL6 and spastin. EMBO J. 2013;32:2920-37 pubmed publisher
    ..Transgenic mice overexpressing Tau show TTLL6 translocalization into dendrites and decreased MT stability. The results provide a rationale for MT stabilization as a therapeutic approach. ..
  6. Yetman M, Jankowsky J. Wild-type neural progenitors divide and differentiate normally in an amyloid-rich environment. J Neurosci. 2013;33:17335-41 pubmed publisher
    ..We tested this hypothesis using a bigenic mouse in which transgenic expression of APP was restricted to mature projection neurons...
  7. Reinert J, Martens H, Huettenrauch M, Kolbow T, Lannfelt L, Ingelsson M, et al. A?38 in the brains of patients with sporadic and familial Alzheimer's disease and transgenic mouse models. J Alzheimers Dis. 2014;39:871-81 pubmed publisher
    ..Furthermore we demonstrate that A?38 deposits in the form of extracellular plaques are common in several AD transgenic mouse models carrying either only A?PP, or combinations of A?PP, PSEN1, and tau transgenes. ..
  8. Rijal Upadhaya A, Kosterin I, Kumar S, von Arnim C, Yamaguchi H, Fändrich M, et al. Biochemical stages of amyloid-? peptide aggregation and accumulation in the human brain and their association with symptomatic and pathologically preclinical Alzheimer's disease. Brain. 2014;137:887-903 pubmed publisher
  9. Kwak Y, Hendrix B, Sugaya K. Secreted type of amyloid precursor protein induces glial differentiation by stimulating the BMP/Smad signaling pathway. Biochem Biophys Res Commun. 2014;447:394-9 pubmed publisher
    ..peptides has been intensively studied within pathophysiology of AD, the physiological function of amyloid precursor protein (APP) still remains unclarified...
  10. Miyazaki T, Ikeda K, Horie Inoue K, Inoue S. Amyloid precursor protein regulates migration and metalloproteinase gene expression in prostate cancer cells. Biochem Biophys Res Commun. 2014;452:828-33 pubmed publisher
    b>Amyloid precursor protein (APP) is a type I transmembrane protein, and one of its processed forms, β-amyloid, is considered to play a central role in the development of Alzheimer's disease...
  11. Cao X, Sudhof T. Dissection of amyloid-beta precursor protein-dependent transcriptional transactivation. J Biol Chem. 2004;279:24601-11 pubmed
    Amyloid-beta precursor protein (APP) forms a transcriptionally active complex with the adaptor protein Fe65 and the histone acetyltransferase Tip60, but the mechanism of transcriptional activation that is mediated by APP and Fe65 remains ..
  12. Shankar G, Leissring M, Adame A, Sun X, Spooner E, Masliah E, et al. Biochemical and immunohistochemical analysis of an Alzheimer's disease mouse model reveals the presence of multiple cerebral Abeta assembly forms throughout life. Neurobiol Dis. 2009;36:293-302 pubmed publisher
    The amyloid beta-protein (Abeta) is believed to play a causal role in Alzheimer's disease, however, the mechanism by which Abeta mediates its effect and the assembly form(s) of Abeta responsible remain unclear...
  13. Lauritzen I, Pardossi Piquard R, Bauer C, Brigham E, Abraham J, Ranaldi S, et al. The β-secretase-derived C-terminal fragment of βAPP, C99, but not Aβ, is a key contributor to early intraneuronal lesions in triple-transgenic mouse hippocampus. J Neurosci. 2012;32:16243-1655a pubmed publisher
    Triple-transgenic mice (3xTgAD) overexpressing Swedish-mutated β-amyloid precursor protein (βAPP(swe)), P310L-Tau (Tau(P301L)), and physiological levels of M146V-presenilin-1 (PS1(M146V)) display extracellular amyloid-β peptides ..
  14. Soba P, Eggert S, Wagner K, Zentgraf H, Siehl K, Kreger S, et al. Homo- and heterodimerization of APP family members promotes intercellular adhesion. EMBO J. 2005;24:3624-34 pubmed
    The amyloid precursor protein (APP) plays a central role in Alzheimer's disease, but its physiological function and that of its mammalian paralogs, the amyloid precursor-like proteins 1 and 2 (APLPs), is still poorly understood...
  15. Biswas S, Shi Y, Vonsattel J, Leung C, Troy C, Greene L. Bim is elevated in Alzheimer's disease neurons and is required for beta-amyloid-induced neuronal apoptosis. J Neurosci. 2007;27:893-900 pubmed
    ..We report that beta-amyloid (Abeta), a death-promoting peptide implicated in the pathophysiology of AD, induces the proapoptotic protein Bcl-2 ..
  16. Neumann S, Schöbel S, Jäger S, Trautwein A, Haass C, Pietrzik C, et al. Amyloid precursor-like protein 1 influences endocytosis and proteolytic processing of the amyloid precursor protein. J Biol Chem. 2006;281:7583-94 pubmed
    Ectodomain shedding of the amyloid precursor protein (APP) is a key regulatory step in the generation of the Alzheimer disease amyloid beta peptide (Abeta)...
  17. Fein J, Sokolow S, Miller C, Vinters H, Yang F, Cole G, et al. Co-localization of amyloid beta and tau pathology in Alzheimer's disease synaptosomes. Am J Pathol. 2008;172:1683-92 pubmed publisher
    The amyloid cascade hypothesis proposes that amyloid beta (Abeta) pathology precedes and induces tau pathology, but the neuropathological connection between these two lesions has not been demonstrated...
  18. Murrell J, Farlow M, Ghetti B, Benson M. A mutation in the amyloid precursor protein associated with hereditary Alzheimer's disease. Science. 1991;254:97-9 pubmed
    ..disease revealed a single amino acid substitution (Phe for Val) in the transmembrane domain of the amyloid precursor protein. This mutation correlates with the presence of Alzheimer's disease in all patients in this study, and ..
  19. Borg J, Ooi J, Levy E, Margolis B. The phosphotyrosine interaction domains of X11 and FE65 bind to distinct sites on the YENPTY motif of amyloid precursor protein. Mol Cell Biol. 1996;16:6229-41 pubmed
    ..of X11 and one of the PI domains of FE65, two neuronal proteins, bind to the cytoplasmic domain of the amyloid precursor protein ((beta)APP). (beta)APP is an integral transmembrane glycoprotein whose cellular function is unknown...
  20. Lacor P, Buniel M, Chang L, Fernandez S, Gong Y, Viola K, et al. Synaptic targeting by Alzheimer's-related amyloid beta oligomers. J Neurosci. 2004;24:10191-200 pubmed
    ..For many years, this dementia was attributed to nerve-cell death induced by deposits of fibrillar amyloid beta (Abeta)...
  21. Zhao G, Mao G, Tan J, Dong Y, Cui M, Kim S, et al. Identification of a new presenilin-dependent zeta-cleavage site within the transmembrane domain of amyloid precursor protein. J Biol Chem. 2004;279:50647-50 pubmed
    Gamma-secretase cleavage of beta-amyloid precursor protein (APP) is crucial in the pathogenesis of Alzheimer disease, because it is the decisive step in the formation of the C terminus of beta-amyloid protein (Abeta)...
  22. Madeira A, Pommet J, Prochiantz A, Allinquant B. SET protein (TAF1beta, I2PP2A) is involved in neuronal apoptosis induced by an amyloid precursor protein cytoplasmic subdomain. FASEB J. 2005;19:1905-7 pubmed
    When overexpressed, a short cytoplasmic domain of the amyloid precursor protein (APP), normally unmasked in the brain of Alzheimer's disease patients, activates caspase-3 and induces neuronal death...
  23. Qiu W, Walsh D, Ye Z, Vekrellis K, Zhang J, Podlisny M, et al. Insulin-degrading enzyme regulates extracellular levels of amyloid beta-protein by degradation. J Biol Chem. 1998;273:32730-8 pubmed
    Excessive cerebral accumulation of the 42-residue amyloid beta-protein (Abeta) is an early and invariant step in the pathogenesis of Alzheimer's disease...
  24. Lustbader J, Cirilli M, Lin C, Xu H, Takuma K, Wang N, et al. ABAD directly links Abeta to mitochondrial toxicity in Alzheimer's disease. Science. 2004;304:448-52 pubmed
    Mitochondrial dysfunction is a hallmark of beta-amyloid (Abeta)-induced neuronal toxicity in Alzheimer's disease (AD)...
  25. Um J, Strittmatter S. Amyloid-? induced signaling by cellular prion protein and Fyn kinase in Alzheimer disease. Prion. 2013;7:37-41 pubmed publisher
    ..These studies suggest that PrP(C) has a central role in AD pathogenesis and may provide a target for therapeutic intervention in AD. ..
  26. Krako N, Magnifico M, Arese M, Meli G, Forte E, Lecci A, et al. Characterization of mitochondrial dysfunction in the 7PA2 cell model of Alzheimer's disease. J Alzheimers Dis. 2013;37:747-58 pubmed publisher
    ..All functional parameters point to a severe bioenergetic impairment of the AD cells, with the extent of mitochondrial dysfunction being correlated to the accumulation of A? peptides and oligomers. ..
  27. Lee J, Retamal C, Cuitino L, Caruano Yzermans A, Shin J, van Kerkhof P, et al. Adaptor protein sorting nexin 17 regulates amyloid precursor protein trafficking and processing in the early endosomes. J Biol Chem. 2008;283:11501-8 pubmed publisher
    Accumulation of extracellular amyloid beta peptide (Abeta), generated from amyloid precursor protein (APP) processing by beta- and gamma-secretases, is toxic to neurons and is central to the pathogenesis of Alzheimer disease...
  28. Copanaki E, Chang S, Vlachos A, Tschäpe J, Müller U, Kogel D, et al. sAPPalpha antagonizes dendritic degeneration and neuron death triggered by proteasomal stress. Mol Cell Neurosci. 2010;44:386-93 pubmed publisher
    ..Here we investigated the biological properties of the secreted cleavage product of APP (sAPPalpha) in antagonizing stress signalling, dendritic degeneration and neuronal cell death induced by the ..
  29. Maulik M, Ghoshal B, Kim J, Wang Y, Yang J, Westaway D, et al. Mutant human APP exacerbates pathology in a mouse model of NPC and its reversal by a ?-cyclodextrin. Hum Mol Genet. 2012;21:4857-75 pubmed publisher
    ..enhanced cholesterol level, which acts as a risk factor for AD, can increase A? production by regulating amyloid precursor protein (APP) metabolism, it is possible that APP overexpression can influence cholesterol-regulated NPC ..
  30. Kuperstein I, Broersen K, Benilova I, Rozenski J, Jonckheere W, Debulpaep M, et al. Neurotoxicity of Alzheimer's disease A? peptides is induced by small changes in the A?42 to A?40 ratio. EMBO J. 2010;29:3408-20 pubmed publisher
    ..Our work also suggests the dynamic nature of the equilibrium between toxic and non-toxic intermediates. ..
  31. Takeda S, Hashimoto T, Roe A, Hori Y, Spires Jones T, Hyman B. Brain interstitial oligomeric amyloid ? increases with age and is resistant to clearance from brain in a mouse model of Alzheimer's disease. FASEB J. 2013;27:3239-48 pubmed publisher
    ..microdialysis, we characterized soluble A? oligomers in brain interstitial fluid (ISF) of awake, freely moving APP/PS1 transgenic and control WT mice...
  32. Shankar G, Bloodgood B, Townsend M, Walsh D, Selkoe D, Sabatini B. Natural oligomers of the Alzheimer amyloid-beta protein induce reversible synapse loss by modulating an NMDA-type glutamate receptor-dependent signaling pathway. J Neurosci. 2007;27:2866-75 pubmed
    ..Although considerable evidence supports a causal role for the amyloid-beta protein (Abeta) in AD, a direct link between a specific form of Abeta and synapse loss has not been established...
  33. Levy E, Carman M, Fernandez Madrid I, Power M, Lieberburg I, van Duinen S, et al. Mutation of the Alzheimer's disease amyloid gene in hereditary cerebral hemorrhage, Dutch type. Science. 1990;248:1124-6 pubmed
    ..The mutation may account for the deposition of this amyloid protein in the cerebral vessel walls of these patients, leading to cerebral hemorrhages and premature death. ..
  34. Sticht H, Bayer P, Willbold D, Dames S, Hilbich C, Beyreuther K, et al. Structure of amyloid A4-(1-40)-peptide of Alzheimer's disease. Eur J Biochem. 1995;233:293-8 pubmed
    ..The sequence of the helical part of prion proteins was observed to be remarkably similar to the sequence of the helical part of human A4-(1-40)-peptide. ..
  35. Rossjohn J, Cappai R, Feil S, Henry A, McKinstry W, Galatis D, et al. Crystal structure of the N-terminal, growth factor-like domain of Alzheimer amyloid precursor protein. Nat Struct Biol. 1999;6:327-31 pubmed
    b>Amyloid precursor protein (APP) plays a central role in Alzheimer disease. A proteolytic-breakdown product of APP, called beta-amyloid, is a major component of the diffuse and fibrillar deposits found in Alzheimer diseased brains...
  36. Rajendran L, Honsho M, Zahn T, Keller P, Geiger K, Verkade P, et al. Alzheimer's disease beta-amyloid peptides are released in association with exosomes. Proc Natl Acad Sci U S A. 2006;103:11172-7 pubmed
    ..The Abeta peptide is formed by the amyloidogenic cleavage of the amyloid precursor protein (APP) by beta- and gamma-secretases...
  37. Wakutani Y, Watanabe K, Adachi Y, Wada Isoe K, Urakami K, Ninomiya H, et al. Novel amyloid precursor protein gene missense mutation (D678N) in probable familial Alzheimer's disease. J Neurol Neurosurg Psychiatry. 2004;75:1039-42 pubmed
    To describe a novel missense mutation, Asp678Asn (D678N), in the amyloid precursor protein (APP) gene in a Japanese pedigree of probable familial Alzheimer's disease (FAD). The proband was a women of 72...
  38. Campion D, Dumanchin C, Hannequin D, Dubois B, Belliard S, Puel M, et al. Early-onset autosomal dominant Alzheimer disease: prevalence, genetic heterogeneity, and mutation spectrum. Am J Hum Genet. 1999;65:664-70 pubmed
    ..2 and 5.3, respectively. We then performed a mutational analysis of the genes for amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) in 34 families with ADEOAD ascertained in France...
  39. Barrett P, Song Y, Van Horn W, Hustedt E, Schafer J, Hadziselimovic A, et al. The amyloid precursor protein has a flexible transmembrane domain and binds cholesterol. Science. 2012;336:1168-71 pubmed publisher
    C99 is the transmembrane carboxyl-terminal domain of the amyloid precursor protein that is cleaved by ?-secretase to release the amyloid-? polypeptides, which are associated with Alzheimer's disease...
  40. Chen S, Yadav S, Surewicz W. Interaction between human prion protein and amyloid-beta (Abeta) oligomers: role OF N-terminal residues. J Biol Chem. 2010;285:26377-83 pubmed publisher
    ..the role of PrP codon 129 polymorphism as a risk factor in AD is due to factors unrelated to the interaction with Abeta oligomers...
  41. Guardia Laguarta C, Coma M, Pera M, Clarimon J, Sereno L, Agulló J, et al. Mild cholesterol depletion reduces amyloid-beta production by impairing APP trafficking to the cell surface. J Neurochem. 2009;110:220-30 pubmed publisher
    It has been suggested that cellular cholesterol levels can modulate the metabolism of the amyloid precursor protein (APP) but the underlying mechanism remains controversial...
  42. Uemura K, Lill C, Li X, Peters J, Ivanov A, Fan Z, et al. Allosteric modulation of PS1/gamma-secretase conformation correlates with amyloid beta(42/40) ratio. PLoS ONE. 2009;4:e7893 pubmed publisher
    ..that target either gamma-secretase components (PS1, Pen2, Aph1) or gamma-secretase substrate (amyloid precursor protein, APP) and are known to change Abeta(42) production are associated with a consistent conformational ..
  43. Sagare A, Deane R, Bell R, Johnson B, Hamm K, Pendu R, et al. Clearance of amyloid-beta by circulating lipoprotein receptors. Nat Med. 2007;13:1029-31 pubmed
    Low-density lipoprotein receptor-related protein-1 (LRP) on brain capillaries clears amyloid beta-peptide (Abeta) from brain...
  44. Williams A, Portelius E, Kheterpal I, Guo J, Cook K, Xu Y, et al. Mapping abeta amyloid fibril secondary structure using scanning proline mutagenesis. J Mol Biol. 2004;335:833-42 pubmed
    Although the amyloid fibrils formed from the Alzheimer's disease amyloid peptide Abeta are rich in cross-beta sheet, the peptide likely also exhibits turn and unstructured regions when it becomes incorporated into amyloid...
  45. Schettini G, Govoni S, Racchi M, Rodriguez G. Phosphorylation of APP-CTF-AICD domains and interaction with adaptor proteins: signal transduction and/or transcriptional role--relevance for Alzheimer pathology. J Neurochem. 2010;115:1299-308 pubmed publisher
    In recent decades, the study of the amyloid precursor protein (APP) and of its proteolytic products carboxy terminal fragment (CTF), APP intracellular C-terminal domain (AICD) and amyloid beta has been mostly focussed on the role of APP ..
  46. Vetrivel K, Thinakaran G. Amyloidogenic processing of beta-amyloid precursor protein in intracellular compartments. Neurology. 2006;66:S69-73 pubmed
    Trafficking and proteolytic processing of amyloid precursor protein (APP) have been the focus of numerous investigations in the past two decades, since the identification of Abeta as the principal component of brain senile plaques and ..
  47. Konig G, Mönning U, Czech C, Prior R, Banati R, Schreiter Gasser U, et al. Identification and differential expression of a novel alternative splice isoform of the beta A4 amyloid precursor protein (APP) mRNA in leukocytes and brain microglial cells. J Biol Chem. 1992;267:10804-9 pubmed
    The gene for the beta A4-amyloid precursor protein (APP) consists of 19 exons which code for a typical N- and O-glycosylated transmembrane protein with four extracellular domains followed by the transmembrane domain and a short ..
  48. Kitazume S, Tachida Y, Kato M, Yamaguchi Y, Honda T, Hashimoto Y, et al. Brain endothelial cells produce amyloid {beta} from amyloid precursor protein 770 and preferentially secrete the O-glycosylated form. J Biol Chem. 2010;285:40097-103 pubmed publisher
    ..Aβ is generated from amyloid precursor protein (APP) by the actions of β- and γ-secretases...
  49. Schmidt V, Sporbert A, Rohe M, Reimer T, Rehm A, Andersen O, et al. SorLA/LR11 regulates processing of amyloid precursor protein via interaction with adaptors GGA and PACS-1. J Biol Chem. 2007;282:32956-64 pubmed
    SorLA has been recognized as a novel sorting receptor that regulates trafficking and processing of the amyloid precursor protein (APP) and that represents a significant risk factor for sporadic Alzheimer disease...
  50. La Fauci G, Lahiri D, Salton S, Robakis N. Characterization of the 5'-end region and the first two exons of the beta-protein precursor gene. Biochem Biophys Res Commun. 1989;159:297-304 pubmed
    ..Human genomic clones encoding the promoter region and the first two exons of the beta-amyloid protein precursor (beta-APP) gene were isolated. The first exon is 205 base pairs (bp) long and encodes 19 amino acids...
  51. Guo J, Arai T, Miklossy J, McGeer P. Abeta and tau form soluble complexes that may promote self aggregation of both into the insoluble forms observed in Alzheimer's disease. Proc Natl Acad Sci U S A. 2006;103:1953-8 pubmed
    ..here by Western blotting and ELISA that a stable complex can form between tau and amyloid-beta protein (Abeta)...
  52. Matrone C, Barbagallo A, La Rosa L, Florenzano F, Ciotti M, Mercanti D, et al. APP is phosphorylated by TrkA and regulates NGF/TrkA signaling. J Neurosci. 2011;31:11756-61 pubmed publisher
    The pathogenic model of Alzheimer's disease (AD) posits that aggregates of amyloid ?, a product of amyloid precursor protein (APP) processing, cause dementia...
  53. Chow N, Korenberg J, Chen X, Neve R. APP-BP1, a novel protein that binds to the carboxyl-terminal region of the amyloid precursor protein. J Biol Chem. 1996;271:11339-46 pubmed
    ..b>APP is a cell surface protein with a large extracellular amino-terminal domain, a single transmembrane segment, and a ..
  54. Tarr P, Roncarati R, Pelicci G, Pelicci P, D ADAMIO L. Tyrosine phosphorylation of the beta-amyloid precursor protein cytoplasmic tail promotes interaction with Shc. J Biol Chem. 2002;277:16798-804 pubmed
    beta-Amyloid precursor protein (APP) is a widely expressed transmembrane protein of unknown function that is involved in the pathogenesis of Alzheimer's disease...
  55. Eckman E, Watson M, Marlow L, Sambamurti K, Eckman C. Alzheimer's disease beta-amyloid peptide is increased in mice deficient in endothelin-converting enzyme. J Biol Chem. 2003;278:2081-4 pubmed
    The abnormal accumulation of beta-amyloid (Abeta) in the brain is an early and invariant feature in Alzheimer's disease (AD) and is believed to play a pivotal role in the etiology and pathogenesis of the disease...
  56. Lashuel H, Hartley D, Petre B, Wall J, Simon M, Walz T, et al. Mixtures of wild-type and a pathogenic (E22G) form of Abeta40 in vitro accumulate protofibrils, including amyloid pores. J Mol Biol. 2003;332:795-808 pubmed
    ..These studies revealed that the Arctic mutation accelerates both Abeta oligomerization and fibrillogenesis in vitro...
  57. Greenwald J, Riek R. Biology of amyloid: structure, function, and regulation. Structure. 2010;18:1244-60 pubmed publisher
    ..In particular, we propose that amyloids could have existed in a prebiotic world, and may have been the first functional protein fold in living cells. ..
  58. Cohen R, Rezai Zadeh K, Weitz T, Rentsendorj A, Gate D, Spivak I, et al. A transgenic Alzheimer rat with plaques, tau pathology, behavioral impairment, oligomeric a?, and frank neuronal loss. J Neurosci. 2013;33:6245-56 pubmed publisher
    ..We have developed a Tg rat model (line TgF344-AD) expressing mutant human amyloid precursor protein (APPsw) and presenilin 1 (PS1?E9) genes, each independent causes of early-onset familial AD...
  59. Preece P, Virley D, Costandi M, Coombes R, Moss S, Mudge A, et al. Amyloid precursor protein mRNA levels in Alzheimer's disease brain. Brain Res Mol Brain Res. 2004;122:1-9 pubmed
    ..deposits in Alzheimer's disease (AD) brain are proteolytically derived from the membrane bound amyloid precursor protein (APP)...
  60. Vassar R, Bennett B, Babu Khan S, Kahn S, Mendiaz E, Denis P, et al. Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE. Science. 1999;286:735-41 pubmed
    ..Abeta generation depends on proteolytic cleavage of the amyloid precursor protein (APP) by two unknown proteases: beta-secretase and gamma-secretase...
  61. Roncarati R, Sestan N, Scheinfeld M, Berechid B, Lopez P, Meucci O, et al. The gamma-secretase-generated intracellular domain of beta-amyloid precursor protein binds Numb and inhibits Notch signaling. Proc Natl Acad Sci U S A. 2002;99:7102-7 pubmed
    The beta-amyloid precursor protein (APP) and the Notch receptor undergo intramembranous proteolysis by the Presenilin-dependent gamma-secretase...
  62. Blom E, Viswanathan J, Kilander L, Helisalmi S, Soininen H, Lannfelt L, et al. Low prevalence of APP duplications in Swedish and Finnish patients with early-onset Alzheimer's disease. Eur J Hum Genet. 2008;16:171-5 pubmed
    ..angiopathy (EOAD/CAA) was recently associated with duplications of the gene for the amyloid-beta precursor protein (APP). In this study, we have screened for duplications of APP in patients with EOAD from Sweden and Finland...
  63. Naruse S, Igarashi S, Kobayashi H, Aoki K, Inuzuka T, Kaneko K, et al. Mis-sense mutation Val----Ile in exon 17 of amyloid precursor protein gene in Japanese familial Alzheimer's disease. Lancet. 1991;337:978-9 pubmed
  64. Lemaire H, Salbaum J, Multhaup G, Kang J, Bayney R, Unterbeck A, et al. The PreA4(695) precursor protein of Alzheimer's disease A4 amyloid is encoded by 16 exons. Nucleic Acids Res. 1989;17:517-22 pubmed
    ..Sequence analysis of the various clones revealed 16 exons to encode the 695 residue precursor protein (PreA4(695] of Alzheimer's disease amyloid A4 protein...
  65. Bhalla A, Vetanovetz C, Morel E, Chamoun Z, Di Paolo G, Small S. The location and trafficking routes of the neuronal retromer and its role in amyloid precursor protein transport. Neurobiol Dis. 2012;47:126-34 pubmed publisher
    ..transport, is highly expressed in the hippocampus, and has been implicated in the trafficking of the amyloid precursor protein (APP)...
  66. Zhang H, Ma Q, Zhang Y, Xu H. Proteolytic processing of Alzheimer's β-amyloid precursor protein. J Neurochem. 2012;120 Suppl 1:9-21 pubmed publisher
    b>Amyloid precursor protein (APP) is a critical factor in the pathogenesis of Alzheimer's disease (AD). APP undergoes post-translational proteolysis/processing to generate the hydrophobic β-amyloid (Aβ) peptides...
  67. Kimberly W, Zheng J, Guenette S, Selkoe D. The intracellular domain of the beta-amyloid precursor protein is stabilized by Fe65 and translocates to the nucleus in a notch-like manner. J Biol Chem. 2001;276:40288-92 pubmed
    The beta-amyloid precursor protein (APP) is a ubiquitous receptor-like molecule without a known function...
  68. Wurth C, Guimard N, Hecht M. Mutations that reduce aggregation of the Alzheimer's Abeta42 peptide: an unbiased search for the sequence determinants of Abeta amyloidogenesis. J Mol Biol. 2002;319:1279-90 pubmed
    ..Although the amino acid residue sequence of Abeta42 is known, the molecular determinants of Abeta amyloidogenesis have not been elucidated...
  69. Zheng W, Xin N, Chi Z, Zhao B, Zhang J, Li J, et al. Divalent metal transporter 1 is involved in amyloid precursor protein processing and Abeta generation. FASEB J. 2009;23:4207-17 pubmed publisher
    The amyloid-beta precursor protein (APP) and its pathogenic byproduct beta-amyloid peptide (Abeta) play central roles in the pathogenesis of Alzheimer's disease (AD)...
  70. Coles M, Bicknell W, Watson A, Fairlie D, Craik D. Solution structure of amyloid beta-peptide(1-40) in a water-micelle environment. Is the membrane-spanning domain where we think it is?. Biochemistry. 1998;37:11064-77 pubmed
    ..is provided in support of a possible new location for the transmembrane domain of Abeta within the amyloid precursor protein (APP). Studies between pH 4.2 and 7.9 reveal a pH-dependent helix-coil conformational switch...
  71. Arancio O, Zhang H, Chen X, Lin C, Trinchese F, Puzzo D, et al. RAGE potentiates Abeta-induced perturbation of neuronal function in transgenic mice. EMBO J. 2004;23:4096-105 pubmed
    ..environment, employing transgenics (Tgs) with targeted neuronal overexpression of RAGE and mutant amyloid precursor protein (APP)...
  72. Bellingham S, Lahiri D, Maloney B, La Fontaine S, Multhaup G, Camakaris J. Copper depletion down-regulates expression of the Alzheimer's disease amyloid-beta precursor protein gene. J Biol Chem. 2004;279:20378-86 pubmed
    ..by the accumulation of amyloid-beta peptide, which is cleaved from the amyloid-beta precursor protein (APP)...
  73. Walker J, Fowler S, Miller D, Sun A, Weisman G, Wood W, et al. Spatial learning and memory impairment and increased locomotion in a transgenic amyloid precursor protein mouse model of Alzheimer's disease. Behav Brain Res. 2011;222:169-75 pubmed publisher
    ..of spatial learning and a behavioral assessment of irritability and locomotion in TgCRND8 mice, an amyloid precursor protein transgenic model of Alzheimer's disease...
  74. Pera M, Alcolea D, Sanchez Valle R, Guardia Laguarta C, Colom Cadena M, Badiola N, et al. Distinct patterns of APP processing in the CNS in autosomal-dominant and sporadic Alzheimer disease. Acta Neuropathol. 2013;125:201-13 pubmed publisher
    Autosomal-dominant Alzheimer disease (ADAD) is a genetic disorder caused by mutations in Amyloid Precursor Protein (APP) or Presenilin (PSEN) genes...
  75. Zheng P, Eastman J, Vande Pol S, Pimplikar S. PAT1, a microtubule-interacting protein, recognizes the basolateral sorting signal of amyloid precursor protein. Proc Natl Acad Sci U S A. 1998;95:14745-50 pubmed
    ..b>Amyloid precursor protein (APP), a basolateral protein implicated in the pathogenesis of Alzheimer's disease, contains a tyrosine-..
  76. Wahle T, Thal D, Sastre M, Rentmeister A, Bogdanovic N, Famulok M, et al. GGA1 is expressed in the human brain and affects the generation of amyloid beta-peptide. J Neurosci. 2006;26:12838-46 pubmed
    ..of Alzheimer disease (AD)-associated senile plaques and is generated by sequential cleavage of the beta-amyloid precursor protein (APP) by beta-secretase (BACE1) and gamma-secretase...
  77. Vetrivel K, Zhang X, Meckler X, Cheng H, Lee S, Gong P, et al. Evidence that CD147 modulation of beta-amyloid (Abeta) levels is mediated by extracellular degradation of secreted Abeta. J Biol Chem. 2008;283:19489-98 pubmed publisher
    ..Intramembranous proteolysis of amyloid precursor protein by a multiprotein gamma-secretase complex generates Abeta...
  78. Nikolaev A, McLaughlin T, O Leary D, Tessier Lavigne M. APP binds DR6 to trigger axon pruning and neuron death via distinct caspases. Nature. 2009;457:981-9 pubmed publisher
    ..Here we report that beta-amyloid precursor protein (APP) and death receptor 6 (DR6, also known as TNFRSF21) activate a widespread caspase-dependent self-..
  79. Duce J, Tsatsanis A, Cater M, James S, Robb E, Wikhe K, et al. Iron-export ferroxidase activity of ?-amyloid precursor protein is inhibited by zinc in Alzheimer's disease. Cell. 2010;142:857-67 pubmed publisher
    ..We found that the AD ?-amyloid protein precursor (APP) possesses ferroxidase activity mediated by a conserved H-ferritin-like active site, which is inhibited ..
  80. Jonsson T, Atwal J, Steinberg S, Snaedal J, Jonsson P, Bjornsson S, et al. A mutation in APP protects against Alzheimer's disease and age-related cognitive decline. Nature. 2012;488:96-9 pubmed publisher
    ..3). Here, to search for low-frequency variants in the amyloid-? precursor protein (APP) gene with a significant effect on the risk of Alzheimer's disease, we studied coding variants in APP in a set of ..
  81. Muresan Z, Muresan V. A phosphorylated, carboxy-terminal fragment of beta-amyloid precursor protein localizes to the splicing factor compartment. Hum Mol Genet. 2004;13:475-88 pubmed
    Beta-amyloid precursor protein (APP) is implicated in the pathobiology of Alzheimer's disease (AD)...
  82. Li Y, Zhou W, Tong Y, He G, Song W. Control of APP processing and Abeta generation level by BACE1 enzymatic activity and transcription. FASEB J. 2006;20:285-92 pubmed
    Deposition of amyloid beta protein (Abeta) is one of the characteristic features of Alzheimer's disease (AD) neuropathology. Beta-secretase, a beta-site APP cleaving enzyme 1 (BACE1), is essential for Abeta biosynthesis...
  83. Jack C, Vemuri P, Wiste H, Weigand S, Aisen P, Trojanowski J, et al. Evidence for ordering of Alzheimer disease biomarkers. Arch Neurol. 2011;68:1526-35 pubmed publisher
  84. Lashuel H, Hartley D, Petre B, Walz T, Lansbury P. Neurodegenerative disease: amyloid pores from pathogenic mutations. Nature. 2002;418:291 pubmed
  85. Cho H, Cahill C, Vanderburg C, Scherzer C, Wang B, Huang X, et al. Selective translational control of the Alzheimer amyloid precursor protein transcript by iron regulatory protein-1. J Biol Chem. 2010;285:31217-32 pubmed publisher
    Iron influx increases the translation of the Alzheimer amyloid precursor protein (APP) via an iron-responsive element (IRE) RNA stem loop in its 5'-untranslated region...
  86. Lesne S, Koh M, Kotilinek L, Kayed R, Glabe C, Yang A, et al. A specific amyloid-beta protein assembly in the brain impairs memory. Nature. 2006;440:352-7 pubmed
    ..Tg2576 mice are caused by the extracellular accumulation of a 56-kDa soluble amyloid-beta assembly, which we term Abeta*56 (Abeta star 56)...
  87. Gorman P, Kim S, Guo M, Melnyk R, McLaurin J, Fraser P, et al. Dimerization of the transmembrane domain of amyloid precursor proteins and familial Alzheimer's disease mutants. BMC Neurosci. 2008;9:17 pubmed publisher
    b>Amyloid precursor protein (APP) is enzymatically cleaved by gamma-secretase to form two peptide products, either Abeta40 or the more neurotoxic Abeta42...