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. 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)...
  2. 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...
  3. 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.
  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-? 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, ?-amyloid, is considered to play a central role in the development of Alzheimer's disease...

Detail Information

Publications112 found, 100 shown here

  1. 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)...
  2. 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...
  3. 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.
  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-? 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, ?-amyloid, is considered to play a central role in the development of Alzheimer's disease...
  11. Finckh U, Müller Thomsen T, Mann U, Eggers C, Marksteiner J, Meins W, et al. High prevalence of pathogenic mutations in patients with early-onset dementia detected by sequence analyses of four different genes. Am J Hum Genet. 2000;66:110-7 pubmed
    ..Mutations in the genes encoding the presenilins (PS1 and PS2) and amyloid precursor protein (APP) are associated with FAD, whereas mutations in the prion protein (PrP) gene are associated with ..
  12. Okochi M, Fukumori A, Jiang J, Itoh N, Kimura R, Steiner H, et al. Secretion of the Notch-1 Abeta-like peptide during Notch signaling. J Biol Chem. 2006;281:7890-8 pubmed
    ..require an additional cleavage near the middle of the transmembrane domain, extracellular small peptides (Notch-1 Abeta-like peptide (Nbeta)) should be produced...
  13. Umeda T, Tomiyama T, Sakama N, Tanaka S, Lambert M, Klein W, et al. Intraneuronal amyloid ? oligomers cause cell death via endoplasmic reticulum stress, endosomal/lysosomal leakage, and mitochondrial dysfunction in vivo. J Neurosci Res. 2011;89:1031-42 pubmed publisher
    ..Previously, we showed that the E693? mutation (referred to as the "Osaka" mutation) of amyloid precursor protein (APP) caused intracellular accumulation of A? oligomers and apoptosis in transfected COS-7 cells...
  14. Kamal A, Stokin G, Yang Z, Xia C, Goldstein L. Axonal transport of amyloid precursor protein is mediated by direct binding to the kinesin light chain subunit of kinesin-I. Neuron. 2000;28:449-59 pubmed
    We analyzed the mechanism of axonal transport of the amyloid precursor protein (APP), which plays a major role in the development of Alzheimer's disease...
  15. Gianni D, Zambrano N, Bimonte M, Minopoli G, Mercken L, Talamo F, et al. Platelet-derived growth factor induces the beta-gamma-secretase-mediated cleavage of Alzheimer's amyloid precursor protein through a Src-Rac-dependent pathway. J Biol Chem. 2003;278:9290-7 pubmed
    The beta-amyloid peptide (Abeta) present in the senile plaques of Alzheimer's disease derives from the cleavage of a membrane protein, named APP, driven by two enzymes, known as beta- and gamma-secretases...
  16. Li H, Wang Z, Wang B, Guo Q, Dolios G, Tabuchi K, et al. Genetic dissection of the amyloid precursor protein in developmental function and amyloid pathogenesis. J Biol Chem. 2010;285:30598-605 pubmed publisher
    Proteolytic processing of the amyloid precursor protein (APP) generates large soluble APP derivatives, ?-amyloid (A?) peptides, and APP intracellular domain...
  17. Gervais F, Xu D, Robertson G, Vaillancourt J, Zhu Y, Huang J, et al. Involvement of caspases in proteolytic cleavage of Alzheimer's amyloid-beta precursor protein and amyloidogenic A beta peptide formation. Cell. 1999;97:395-406 pubmed
    The amyloid-beta precursor protein (APP) is directly and efficiently cleaved by caspases during apoptosis, resulting in elevated amyloid-beta (A beta) peptide formation...
  18. Shivaprasad S, Wetzel R. Scanning cysteine mutagenesis analysis of Abeta-(1-40) amyloid fibrils. J Biol Chem. 2006;281:993-1000 pubmed
    We describe here the use of cysteine substitution mutants in the Alzheimer disease amyloid plaque peptide Abeta-(1-40) to probe amyloid fibril structure and stabilization...
  19. Gimbel D, Nygaard H, Coffey E, Gunther E, Lauren J, Gimbel Z, et al. Memory impairment in transgenic Alzheimer mice requires cellular prion protein. J Neurosci. 2010;30:6367-74 pubmed publisher
    Soluble oligomers of the amyloid-beta (Abeta) peptide are thought to play a key role in the pathophysiology of Alzheimer's disease (AD)...
  20. Ovchinnikova O, Finder V, Vodopivec I, Nitsch R, Glockshuber R. The Osaka FAD mutation E22? leads to the formation of a previously unknown type of amyloid ? fibrils and modulates A? neurotoxicity. J Mol Biol. 2011;408:780-91 pubmed publisher
    ..Because A?1-40 is the major A? form in vivo, the gain of toxic function caused by the E22 deletion may explain the development of familial AD in mutation carriers. ..
  21. Ray B, Long J, Sokol D, Lahiri D. Increased secreted amyloid precursor protein-? (sAPP?) in severe autism: proposal of a specific, anabolic pathway and putative biomarker. PLoS ONE. 2011;6:e20405 pubmed publisher
    ..Here we further tested the hypothesis that levels of sAPP? and sAPP? (proteolytic cleavage products of APP by ?- and ?-secretase, respectively) are deranged in autism and may contribute to an anabolic environment leading ..
  22. Busciglio J, Pelsman A, Wong C, Pigino G, Yuan M, Mori H, et al. Altered metabolism of the amyloid beta precursor protein is associated with mitochondrial dysfunction in Down's syndrome. Neuron. 2002;33:677-88 pubmed
    ..Thus, mitochondrial dysfunction in DS may lead to intracellular deposition of Abeta42, reduced levels of AbetaPPs, and a chronic state of increased neuronal vulnerability. ..
  23. Hoshino T, Nakaya T, Araki W, Suzuki K, Suzuki T, Mizushima T. Endoplasmic reticulum chaperones inhibit the production of amyloid-beta peptides. Biochem J. 2007;402:581-9 pubmed
    Abeta (amyloid-beta peptides) generated by proteolysis of APP (beta-amyloid precursor protein), play an important role in the pathogenesis of AD (Alzheimer's disease)...
  24. Scacchi R, Gambina G, Moretto G, Corbo R. A mutation screening by DHPLC of PSEN1 and APP genes reveals no significant variation associated with the sporadic late-onset form of Alzheimer's disease. Neurosci Lett. 2007;418:282-5 pubmed
    ..The familial form has often been reportedly caused by mutations in amyloid precursor protein (APP), presenilin-1 (PSEN1), or presenilin-2 (PSEN2) genes, whereas the genetic component for the ..
  25. Simón A, Schiapparelli L, Salazar Colocho P, Cuadrado Tejedor M, Escribano L, Lopez de Maturana R, et al. Overexpression of wild-type human APP in mice causes cognitive deficits and pathological features unrelated to Abeta levels. Neurobiol Dis. 2009;33:369-78 pubmed publisher
    Transgenic mice expressing mutant human amyloid precursor protein (APP) develop an age-dependent amyloid pathology and memory deficits, but no overt neuronal loss...
  26. Goodger Z, Rajendran L, Trutzel A, Kohli B, Nitsch R, Konietzko U. Nuclear signaling by the APP intracellular domain occurs predominantly through the amyloidogenic processing pathway. J Cell Sci. 2009;122:3703-14 pubmed publisher
    Proteolytic processing of the amyloid precursor protein (APP) occurs via two alternative pathways, localized to different subcellular compartments, which result in functionally distinct outcomes...
  27. Koffie R, Meyer Luehmann M, Hashimoto T, Adams K, Mielke M, Garcia Alloza M, et al. Oligomeric amyloid beta associates with postsynaptic densities and correlates with excitatory synapse loss near senile plaques. Proc Natl Acad Sci U S A. 2009;106:4012-7 pubmed publisher
    ..whether this is caused by fibrillar deposits known as senile plaques or soluble oligomeric forms of amyloid beta (Abeta) is controversial...
  28. Scheinfeld M, Roncarati R, Vito P, Lopez P, Abdallah M, D ADAMIO L. Jun NH2-terminal kinase (JNK) interacting protein 1 (JIP1) binds the cytoplasmic domain of the Alzheimer's beta-amyloid precursor protein (APP). J Biol Chem. 2002;277:3767-75 pubmed
    ..amyloid beta precursor protein (APP) is sequentially processed by beta- and gamma-secretases to generate the Abeta peptide...
  29. Pickford F, Masliah E, Britschgi M, Lucin K, Narasimhan R, Jaeger P, et al. The autophagy-related protein beclin 1 shows reduced expression in early Alzheimer disease and regulates amyloid beta accumulation in mice. J Clin Invest. 2008;118:2190-9 pubmed publisher
    ..In transgenic mice that express human amyloid precursor protein (APP), a model for AD, genetic reduction of Becn1 expression increased intraneuronal amyloid beta (Abeta)..
  30. Dahms S, Hoefgen S, Roeser D, Schlott B, Gührs K, Than M. Structure and biochemical analysis of the heparin-induced E1 dimer of the amyloid precursor protein. Proc Natl Acad Sci U S A. 2010;107:5381-6 pubmed publisher
    The amyloid precursor protein (APP) is the key player in Alzheimer's disease pathology, yet APP and its analogues are also essential for neuronal development and cell homeostasis in mammals...
  31. Yan S, Fu J, Soto C, Chen X, Zhu H, Al Mohanna F, et al. An intracellular protein that binds amyloid-beta peptide and mediates neurotoxicity in Alzheimer's disease. Nature. 1997;389:689-95 pubmed
    ..By interacting with intracellular amyloid-beta, ERAB may therefore contribute to the neuronal dysfunction associated with Alzheimer's disease. ..
  32. Yaar M, Zhai S, Fine R, Eisenhauer P, Arble B, Stewart K, et al. Amyloid beta binds trimers as well as monomers of the 75-kDa neurotrophin receptor and activates receptor signaling. J Biol Chem. 2002;277:7720-5 pubmed
    ..Our data suggest that p75(NTR) may be present as a preformed trimer that binds amyloid beta to induce receptor activation, and support the hypothesis that p75(NTR) activation by amyloid beta is causally related to Alzheimer's disease. ..
  33. King G, Perez R, Steinhilb M, Gaut J, Turner R. X11alpha modulates secretory and endocytic trafficking and metabolism of amyloid precursor protein: mutational analysis of the YENPTY sequence. Neuroscience. 2003;120:143-54 pubmed
    The neuronal adaptor X11alpha interacts with the conserved -GYENPTY- sequence in the C-terminus of amyloid precursor protein (APP) or its Swedish mutation (APPswe) to inhibit Abeta40 and Abeta42 secretion...
  34. Stein T, Anders N, DeCarli C, Chan S, Mattson M, Johnson J. Neutralization of transthyretin reverses the neuroprotective effects of secreted amyloid precursor protein (APP) in APPSW mice resulting in tau phosphorylation and loss of hippocampal neurons: support for the amyloid hypothesis. J Neurosci. 2004;24:7707-17 pubmed
    Alzheimer's disease (AD) may be caused by the abnormal processing of the amyloid precursor protein (APP) and the accumulation of beta-amyloid (Abeta)...
  35. Obici L, Demarchi A, de Rosa G, Bellotti V, Marciano S, Donadei S, et al. A novel AbetaPP mutation exclusively associated with cerebral amyloid angiopathy. Ann Neurol. 2005;58:639-44 pubmed
    Mutations in AbetaPP cause deposition of Abeta amyloid fibrils in brain parenchyma and cerebral vessels, resulting in Alzheimer's disease (AD) and/or cerebral amyloid angiopathy (CAA)...
  36. Matsuda S, Matsuda Y, D ADAMIO L. BRI3 inhibits amyloid precursor protein processing in a mechanistically distinct manner from its homologue dementia gene BRI2. J Biol Chem. 2009;284:15815-25 pubmed publisher
    ..Abeta is cleaved off from amyloid precursor protein (APP) with consecutive proteolytic processing: beta-secretase, followed by gamma-secretase...
  37. Salehi A, Delcroix J, Belichenko P, Zhan K, Wu C, Valletta J, et al. Increased App expression in a mouse model of Down's syndrome disrupts NGF transport and causes cholinergic neuron degeneration. Neuron. 2006;51:29-42 pubmed
    ..We used Ts65Dn and Ts1Cje mouse models of DS to show that the increased dose of the amyloid precursor protein gene, App, acts to markedly decrease NGF retrograde transport and cause degeneration of BFCNs...
  38. Young Pearse T, Chen A, Chang R, Marquez C, Selkoe D. Secreted APP regulates the function of full-length APP in neurite outgrowth through interaction with integrin beta1. Neural Dev. 2008;3:15 pubmed publisher
    Beta-amyloid precursor protein (APP) has been reported to play a role in the outgrowth of neurites from cultured neurons...
  39. di Fede G, Catania M, Morbin M, Rossi G, Suardi S, Mazzoleni G, et al. A recessive mutation in the APP gene with dominant-negative effect on amyloidogenesis. Science. 2009;323:1473-7 pubmed publisher
    beta-Amyloid precursor protein (APP) mutations cause familial Alzheimer's disease with nearly complete penetrance...
  40. Kwak Y, Dantuma E, Merchant S, Bushnev S, Sugaya K. Amyloid-? precursor protein induces glial differentiation of neural progenitor cells by activation of the IL-6/gp130 signaling pathway. Neurotox Res. 2010;18:328-38 pubmed publisher
    Although amyloid precursor protein (APP) due to the cytotoxicity of A? peptides, has been intensively studied, the physiological role of APP still remains wrapped up in veil...
  41. Jensen P, Hojrup P, Hager H, Nielsen M, Jacobsen L, Olesen O, et al. Binding of Abeta to alpha- and beta-synucleins: identification of segments in alpha-synuclein/NAC precursor that bind Abeta and NAC. Biochem J. 1997;323 ( Pt 2):539-46 pubmed
    ..a 35-residue peptide derived from the neuronal protein alpha-synuclein/NAC precursor, is tightly associated with Abeta fibrils in Alzheimer's disease amyloid, and alpha-synuclein has recently been shown to bind Abeta in vitro...
  42. Finckh U, Kuschel C, Anagnostouli M, Patsouris E, Pantes G, Gatzonis S, et al. Novel mutations and repeated findings of mutations in familial Alzheimer disease. Neurogenetics. 2005;6:85-9 pubmed
    ..mutations in PSEN1, PSEN2, and APP, the known FAD genes encoding the presenilins (PS1 and PS2) and the amyloid precursor protein (APP). The mutation detection rate was 57%...
  43. Herl L, Thomas A, Lill C, Banks M, Deng A, Jones P, et al. Mutations in amyloid precursor protein affect its interactions with presenilin/gamma-secretase. Mol Cell Neurosci. 2009;41:166-74 pubmed publisher
    ..Several mutations in presenilin (PS1) and beta-amyloid precursor protein (APP) associate with an increased Abeta(42/40) ratio...
  44. Iijima K, Gatt A, Iijima Ando K. Tau Ser262 phosphorylation is critical for Abeta42-induced tau toxicity in a transgenic Drosophila model of Alzheimer's disease. Hum Mol Genet. 2010;19:2947-57 pubmed publisher
  45. Lanni C, Mazzucchelli M, Porrello E, Govoni S, Racchi M. Differential involvement of protein kinase C alpha and epsilon in the regulated secretion of soluble amyloid precursor protein. Eur J Biochem. 2004;271:3068-75 pubmed
    ..the differential role of protein kinase C (PKC) isoforms in the regulated proteolytic release of soluble amyloid precursor protein (sAPPalpha) in SH-SY5Y neuroblastoma cells...
  46. Muresan Z, Muresan V. Coordinated transport of phosphorylated amyloid-beta precursor protein and c-Jun NH2-terminal kinase-interacting protein-1. J Cell Biol. 2005;171:615-25 pubmed
    The transmembrane protein amyloid-beta precursor protein (APP) and the vesicle-associated protein c-Jun NH(2)-terminal kinase-interacting protein-1 (JIP-1) are transported into axons by kinesin-1...
  47. Alafuzoff I, Thal D, Arzberger T, Bogdanovic N, Al Sarraj S, Bodi I, et al. Assessment of beta-amyloid deposits in human brain: a study of the BrainNet Europe Consortium. Acta Neuropathol. 2009;117:309-20 pubmed publisher
    ..Because most of these blocks are currently routinely sampled by the majority of laboratories, assessment of the A-beta phase in AD is feasible even in large scale retrospective studies. ..
  48. Xue W, Hellewell A, Gosal W, Homans S, Hewitt E, Radford S. Fibril fragmentation enhances amyloid cytotoxicity. J Biol Chem. 2009;284:34272-82 pubmed publisher
  49. Kounnas M, Moir R, Rebeck G, Bush A, Argraves W, Tanzi R, et al. LDL receptor-related protein, a multifunctional ApoE receptor, binds secreted beta-amyloid precursor protein and mediates its degradation. Cell. 1995;82:331-40 pubmed
    The secreted form of beta-amyloid precursor protein (APP) containing the Kunitz proteinase inhibitor (KPI) domain, also called protease nexin II, is internalized and degraded by cells...
  50. Godbolt A, Beck J, Collinge J, Cipolotti L, Fox N, Rossor M. A second family with familial AD and the V717L APP mutation has a later age at onset. Neurology. 2006;66:611-2 pubmed
  51. Haglund M, Kalaria R, Slade J, Englund E. Differential deposition of amyloid beta peptides in cerebral amyloid angiopathy associated with Alzheimer's disease and vascular dementia. Acta Neuropathol. 2006;111:430-5 pubmed
    ..neuronal sources of Abeta peptides are sufficient to cause CAA in transgenic mice overexpressing the amyloid precursor protein, there is reason to believe that in aging man, vascular disease modulates the disease process...
  52. Menendez Gonzalez M, Perez Pinera P, Martinez Rivera M, Calatayud M, Blazquez Menes B. APP processing and the APP-KPI domain involvement in the amyloid cascade. Neurodegener Dis. 2005;2:277-83 pubmed
    Alternative APP mRNA splicing can generate isoforms of APP containing a Kunitz protease inhibitor (KPI) domain. KPI is one of the main serine protease inhibitors...
  53. Schöbel S, Neumann S, Hertweck M, Dislich B, Kuhn P, Kremmer E, et al. A novel sorting nexin modulates endocytic trafficking and alpha-secretase cleavage of the amyloid precursor protein. J Biol Chem. 2008;283:14257-68 pubmed publisher
    Ectodomain shedding of the amyloid precursor protein (APP) by the two proteases alpha- and beta-secretase is a key regulatory event in the generation of the Alzheimer disease amyloid beta peptide (Abeta)...
  54. Kanekiyo T, Bu G. Receptor-associated protein interacts with amyloid-beta peptide and promotes its cellular uptake. J Biol Chem. 2009;284:33352-9 pubmed publisher
    Brain amyloid-beta (Abeta) peptide accumulation and aggregation are critical events in the pathogenesis of Alzheimer disease. Increasing evidence has demonstrated that LRP1 is involved in Alzheimer disease pathogenesis...
  55. Iijima Ando K, Hearn S, Shenton C, Gatt A, Zhao L, Iijima K. Mitochondrial mislocalization underlies Abeta42-induced neuronal dysfunction in a Drosophila model of Alzheimer's disease. PLoS ONE. 2009;4:e8310 pubmed publisher
    ..These results demonstrate that mislocalization of mitochondria underlies the pathogenic effects of Abeta42 in vivo. ..
  56. Bayer T, Paliga K, Weggen S, Wiestler O, Beyreuther K, Multhaup G. Amyloid precursor-like protein 1 accumulates in neuritic plaques in Alzheimer's disease. Acta Neuropathol. 1997;94:519-24 pubmed
    The Alzheimer's disease (AD) beta-amyloid precursor protein (APP) and the amyloid precursor-like protein 1 (APLP1) and 2 (APLP2) are members of a super-family of proteins that appear functionally related...
  57. Annaert W, De Strooper B. A cell biological perspective on Alzheimer's disease. Annu Rev Cell Dev Biol. 2002;18:25-51 pubmed
    The amyloid precursor protein and the proteases cleaving this protein are important players in the pathogenesis of Alzheimer's disease via the generation of the amyloid peptide...
  58. Kerr M, Small D. Cytoplasmic domain of the beta-amyloid protein precursor of Alzheimer's disease: function, regulation of proteolysis, and implications for drug development. J Neurosci Res. 2005;80:151-9 pubmed
    The beta-amyloid protein precursor (APP) has been extensively studied for its role in amyloid production and the pathogenesis of Alzheimer's disease (AD)...
  59. Spoelgen R, von Arnim C, Thomas A, Peltan I, Koker M, Deng A, et al. Interaction of the cytosolic domains of sorLA/LR11 with the amyloid precursor protein (APP) and beta-secretase beta-site APP-cleaving enzyme. J Neurosci. 2006;26:418-28 pubmed
    sorLA is a recently identified neuronal receptor for amyloid precursor protein (APP) that is known to interact with APP and affect its intracellular transport and processing...
  60. Qing H, He G, Ly P, Fox C, Staufenbiel M, Cai F, et al. Valproic acid inhibits Abeta production, neuritic plaque formation, and behavioral deficits in Alzheimer's disease mouse models. J Exp Med. 2008;205:2781-9 pubmed publisher
    ..Amyloid beta-protein (Abeta), the central component of neuritic plaques, is derived from beta-amyloid precursor protein (APP) after beta- and gamma-secretase cleavage...
  61. Cerf E, Sarroukh R, Tamamizu Kato S, Breydo L, Derclaye S, Dufrêne Y, et al. Antiparallel beta-sheet: a signature structure of the oligomeric amyloid beta-peptide. Biochem J. 2009;421:415-23 pubmed publisher
    AD (Alzheimer's disease) is linked to Abeta (amyloid beta-peptide) misfolding. Studies demonstrate that the level of soluble Abeta oligomeric forms correlates better with the progression of the disease than the level of fibrillar forms...
  62. Wang Z, Wang B, Yang L, Guo Q, Aithmitti N, Songyang Z, et al. Presynaptic and postsynaptic interaction of the amyloid precursor protein promotes peripheral and central synaptogenesis. J Neurosci. 2009;29:10788-801 pubmed publisher
    A critical role of the amyloid precursor protein (APP) in Alzheimer's disease (AD) pathogenesis has been well established. However, the physiological function of APP remains elusive and much debated...
  63. Kodam A, Maulik M, Peake K, Amritraj A, Vetrivel K, Thinakaran G, et al. Altered levels and distribution of amyloid precursor protein and its processing enzymes in Niemann-Pick type C1-deficient mouse brains. Glia. 2010;58:1267-81 pubmed publisher
    ..Abeta)-related peptides in vulnerable brain regions, but very little is known about the expression of amyloid precursor protein (APP) or APP secretases in NPC disease...
  64. Sani M, Gehman J, Separovic F. Lipid matrix plays a role in Abeta fibril kinetics and morphology. FEBS Lett. 2011;585:749-54 pubmed publisher
    ..Circular dichroism and thioflavin T assays confirmed an initially unstructured peptide, and measured its transition to an aggregated beta-sheet conformation. ..
  65. Lewis V, Whitehouse I, Baybutt H, Manson J, Collins S, Hooper N. Cellular prion protein expression is not regulated by the Alzheimer's amyloid precursor protein intracellular domain. PLoS ONE. 2012;7:e31754 pubmed publisher
    ..The cellular prion protein, PrP(C), modulates the post-translational processing of the AD amyloid precursor protein (APP), through its inhibition of the ?-secretase BACE1, and oligomers of amyloid-? bind to PrP(C) which ..
  66. Bakker E, Van Broeckhoven C, Haan J, Voorhoeve E, Van Hul W, Levy E, et al. DNA diagnosis for hereditary cerebral hemorrhage with amyloidosis (Dutch type). Am J Hum Genet. 1991;49:518-21 pubmed
    ..cerebral hemorrhage with amyloidosis of the Dutch type (HCHWA-D) is tightly linked to the Alzheimer amyloid precursor protein gene on chromosome 21, which codes for the amyloid beta-protein...
  67. Ray W, Yao M, Mumm J, Schroeter E, Saftig P, Wolfe M, et al. Cell surface presenilin-1 participates in the gamma-secretase-like proteolysis of Notch. J Biol Chem. 1999;274:36801-7 pubmed
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    ..For mice expressing familial AD transgenes, mGluR5 antagonism reverses deficits in learning, memory, and synapse density. Thus, A?o-PrP(C) complexes at the neuronal surface activate mGluR5 to disrupt neuronal function. ..
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    ..Increasing A beta deposition appears to lead to the distortion and occlusion of capillaries, which may contribute significantly to the pathology of Alzheimer disease. ..
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    ..This corresponds to the mutation A713T in APP. AD stage VI of neurofibrillary degeneration and stage C of Abeta-amyloid burden was found at the post-mortem neuropathological examination...
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    b>Abeta accumulation has an important function in the etiology of Alzheimer's disease (AD) with its typical clinical symptoms, like memory impairment and changes in personality...
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    ..CSF A?42, t-tau, and p-tau are useful in differential dementia diagnosis. However, in DLB, FTLD, VaD, and CBD, a substantial group exhibit a CSF AD biomarker profile, which requires more autopsy confirmation in the future. ..
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    Threonine(668) (thr(668)) within the carboxy-terminus of the Alzheimer's disease amyloid precursor protein (APP) is a known in vivo phosphorylation site. Phosphorylation of APPthr(668) is believed to regulate APP function and metabolism...
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