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. Kitaguchi N, Takahashi Y, Tokushima Y, Shiojiri S, Ito H. Novel precursor of Alzheimer's disease amyloid protein shows protease inhibitory activity. Nature. 1988;331:530-2 pubmed
    ..AP) as senile plaque core and vascular amyloid, and a complementary DNA encoding a precursor of this protein (APP) has been cloned from human brain...
  2. 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...
  3. 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...
  4. 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)...
  5. 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...
  6. 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...
  7. 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...
  8. 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)...
  9. 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.

More Information

Publications419 found, 100 shown here

  1. 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...
  2. 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...
  3. 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...
  4. 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)...
  5. 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. ..
  6. 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. ..
  7. 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...
  8. 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. ..
  9. 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
  10. 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...
  11. 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...
  12. 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)...
  13. 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...
  14. 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...
  15. Herskowitz J, Seyfried N, Gearing M, Kahn R, Peng J, Levey A, et al. Rho kinase II phosphorylation of the lipoprotein receptor LR11/SORLA alters amyloid-beta production. J Biol Chem. 2011;286:6117-27 pubmed publisher
    ..LR11 interacts with the amyloid-? precursor protein (APP) and regulates APP traffic and processing to amyloid-? peptide (A?)...
  16. Santosa C, Rasche S, Barakat A, Bellingham S, Ho M, Tan J, et al. Decreased expression of GGA3 protein in Alzheimer's disease frontal cortex and increased co-distribution of BACE with the amyloid precursor protein. Neurobiol Dis. 2011;43:176-83 pubmed publisher
    BACE initiates the amyloidogenic processing of the amyloid precursor protein (APP) that results in the production of A? peptides associated with Alzheimer's disease (AD)...
  17. Maatuk N, Samson A. Modeling the binding mechanism of Alzheimer's A?1-42 to nicotinic acetylcholine receptors based on similarity with snake ?-neurotoxins. Neurotoxicology. 2013;34:236-42 pubmed publisher
  18. Morel E, Chamoun Z, Lasiecka Z, Chan R, Williamson R, Vetanovetz C, et al. Phosphatidylinositol-3-phosphate regulates sorting and processing of amyloid precursor protein through the endosomal system. Nat Commun. 2013;4:2250 pubmed publisher
    ..Silencing Vps34 causes an enlargement of neuronal endosomes, enhances the amyloidogenic processing of amyloid precursor protein in these organelles and reduces amyloid precursor protein sorting to intraluminal vesicles...
  19. Johnson R, Xiao G, Shanmugaratnam J, Fine R. Calreticulin functions as a molecular chaperone for the beta-amyloid precursor protein. Neurobiol Aging. 2001;22:387-95 pubmed
    Processing of the beta-amyloid precursor protein (APP) in the endoplasmic reticulum and the Golgi apparatus may be critical in generating the beta-amyloid molecules linked to the pathogenesis of Alzheimer's disease...
  20. Sola Vigo F, Kedikian G, Heredia L, Heredia F, Añel A, Rosa A, et al. Amyloid-beta precursor protein mediates neuronal toxicity of amyloid beta through Go protein activation. Neurobiol Aging. 2009;30:1379-92 pubmed publisher
    Amyloid beta (Abeta) is a metabolic product of amyloid-beta precursor protein (APP). Deposition of Abeta in the brain and neuronal degeneration are characteristic hallmarks of Alzheimer's disease (AD)...
  21. Ni C, Shi H, Yu H, Chang Y, Chen Y. Folding stability of amyloid-beta 40 monomer is an important determinant of the nucleation kinetics in fibrillization. FASEB J. 2011;25:1390-401 pubmed publisher
    ..Overall, we demonstrated that folding stability of Aβ is an important determinant of the nucleation kinetics. ..
  22. Ancolio K, Dumanchin C, Barelli H, Warter J, Brice A, Campion D, et al. Unusual phenotypic alteration of beta amyloid precursor protein (betaAPP) maturation by a new Val-715 --> Met betaAPP-770 mutation responsible for probable early-onset Alzheimer's disease. Proc Natl Acad Sci U S A. 1999;96:4119-24 pubmed
    We have identified a novel beta amyloid precursor protein (betaAPP) mutation (V715M-betaAPP770) that cosegregates with early-onset Alzheimer's disease (AD) in a pedigree...
  23. Gandy S, Simon A, Steele J, Lublin A, Lah J, Walker L, et al. Days to criterion as an indicator of toxicity associated with human Alzheimer amyloid-beta oligomers. Ann Neurol. 2010;68:220-30 pubmed publisher
    ..of endogenously formed oAbeta/ADDLs generated in situ from the physiological processing of human amyloid precursor protein (APP) and presenitin1 (PS1) transgenes...
  24. Wang H, Lee D, D Andrea M, Peterson P, Shank R, Reitz A. beta-Amyloid(1-42) binds to alpha7 nicotinic acetylcholine receptor with high affinity. Implications for Alzheimer's disease pathology. J Biol Chem. 2000;275:5626-32 pubmed
    ..Using human brain tissues and cells that overexpress either alpha7nAChR or amyloid precursor protein as the starting material, Abeta(1-42) and alpha7nAChR can be co-immunoprecipitated by the respective ..
  25. Sahlin C, Lord A, Magnusson K, Englund H, Almeida C, Greengard P, et al. The Arctic Alzheimer mutation favors intracellular amyloid-beta production by making amyloid precursor protein less available to alpha-secretase. J Neurochem. 2007;101:854-62 pubmed
    Mutations within the amyloid-beta (Abeta) domain of the amyloid precursor protein (APP) typically generate hemorrhagic strokes and vascular amyloid angiopathy. In contrast, the Arctic mutation (APP E693G) results in Alzheimer's disease...
  26. Esparza T, Zhao H, Cirrito J, Cairns N, Bateman R, Holtzman D, et al. Amyloid-? oligomerization in Alzheimer dementia versus high-pathology controls. Ann Neurol. 2013;73:104-19 pubmed publisher
    ..The A? oligomer assay does not recognize monomeric A?, amyloid precursor protein, or other non-A? peptide oligomers...
  27. Scheuermann S, Hambsch B, Hesse L, Stumm J, Schmidt C, Beher D, et al. Homodimerization of amyloid precursor protein and its implication in the amyloidogenic pathway of Alzheimer's disease. J Biol Chem. 2001;276:33923-9 pubmed
    We reported previously that the carbohydrate domain of the amyloid precursor protein is involved in amyloid precursor protein (APP)-APP interactions...
  28. Reinhard C, Hébert S, De Strooper B. The amyloid-beta precursor protein: integrating structure with biological function. EMBO J. 2005;24:3996-4006 pubmed
    Proteolytic processing of the amyloid-beta precursor protein (APP) generates the Abeta amyloid peptide of Alzheimer's disease. The biological function of APP itself remains, however, unclear...
  29. Yu L, Edalji R, Harlan J, Holzman T, Lopez A, Labkovsky B, et al. Structural characterization of a soluble amyloid beta-peptide oligomer. Biochemistry. 2009;48:1870-7 pubmed publisher
    ..Using NMR, we have characterized soluble oligomers of Abeta preglobulomer and globulomer that are stable and alter synaptic activity...
  30. Rodrigue K, Kennedy K, Park D. Beta-amyloid deposition and the aging brain. Neuropsychol Rev. 2009;19:436-50 pubmed publisher
    ..One promising biomarker is beta amyloid (Abeta) deposition...
  31. Niederhoffer N, Levy R, Sick E, Andre P, Coupin G, Lombard Y, et al. Amyloid beta peptides trigger CD47-dependent mast cell secretory and phagocytic responses. Int J Immunopathol Pharmacol. 2009;22:473-83 pubmed
    ..In the present study, we examined mast cell responses to amyloid beta (Abeta) peptides 1-40 and 1-42, the major components of the Alzheimer amyloid plaques...
  32. Gu L, Liu C, Guo Z. Structural insights into A?42 oligomers using site-directed spin labeling. J Biol Chem. 2013;288:18673-83 pubmed publisher
    ..5-12.5 Å. These intermolecular distances rule out the existence of fibril-like parallel in-register ?-structures and strongly suggest an antiparallel ?-sheet arrangement in A?42 globulomers. ..
  33. Broytman O, Westmark P, Gurel Z, Malter J. Rck/p54 interacts with APP mRNA as part of a multi-protein complex and enhances APP mRNA and protein expression in neuronal cell lines. Neurobiol Aging. 2009;30:1962-74 pubmed publisher
    Overproduction of amyloid precursor protein (APP) and beta-amyloid likely contribute to neurodegeneration seen in Alzheimer's disease (AD). APP mRNA contains several, 3'-untranslated region (UTR), cis-acting regulatory elements...
  34. Hansson O, Zetterberg H, Vanmechelen E, Vanderstichele H, Andreasson U, Londos E, et al. Evaluation of plasma Abeta(40) and Abeta(42) as predictors of conversion to Alzheimer's disease in patients with mild cognitive impairment. Neurobiol Aging. 2010;31:357-67 pubmed publisher
    Numerous studies have shown a marked decrease of beta-amyloid(42) (Abeta(42)) in the cerebrospinal fluid (CSF) of patients with incipient Alzheimer's disease (AD)...
  35. Sato T, Kienlen Campard P, Ahmed M, Liu W, Li H, Elliott J, et al. Inhibitors of amyloid toxicity based on beta-sheet packing of Abeta40 and Abeta42. Biochemistry. 2006;45:5503-16 pubmed
    ..Here we show that in Abeta amyloid fibrils, Met35 packs against Gly33 in the C-terminus of Abeta40 and against Gly37 in the C-terminus of ..
  36. Hiltunen M, Lu A, Thomas A, Romano D, Kim M, Jones P, et al. Ubiquilin 1 modulates amyloid precursor protein trafficking and Abeta secretion. J Biol Chem. 2006;281:32240-53 pubmed
    ..Here we present the first assessment of the effects of UBQLN1 on the metabolism of the amyloid precursor protein (APP)...
  37. Paravastu A, Leapman R, Yau W, Tycko R. Molecular structural basis for polymorphism in Alzheimer's beta-amyloid fibrils. Proc Natl Acad Sci U S A. 2008;105:18349-54 pubmed publisher
    ..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...
  38. Caspersen C, Wang N, Yao J, Sosunov A, Chen X, Lustbader J, et al. Mitochondrial Abeta: a potential focal point for neuronal metabolic dysfunction in Alzheimer's disease. FASEB J. 2005;19:2040-1 pubmed
    ..in mitochondria from brains of transgenic mice with targeted neuronal overexpression of mutant human amyloid precursor protein and AD patients...
  39. Leblanc A, Liu H, Goodyer C, Bergeron C, Hammond J. Caspase-6 role in apoptosis of human neurons, amyloidogenesis, and Alzheimer's disease. J Biol Chem. 1999;274:23426-36 pubmed
    ..Abeta is a consequence of neuronal apoptosis, suggesting that apoptosis activates proteases involved in amyloid precursor protein (APP) processing...
  40. Kaden D, Harmeier A, Weise C, Münter L, Althoff V, Rost B, et al. Novel APP/A? mutation K16N produces highly toxic heteromeric A? oligomers. EMBO Mol Med. 2012;4:647-59 pubmed publisher
    Here, we describe a novel missense mutation in the amyloid precursor protein (APP) causing a lysine-to-asparagine substitution at position 687 (APP770; herein, referred to as K16N according to amyloid-? (A?) numbering) resulting in an ..
  41. Murphy M, LeVine H. Alzheimer's disease and the amyloid-beta peptide. J Alzheimers Dis. 2010;19:311-23 pubmed publisher
    ..AD) pathogenesis is widely believed to be driven by the production and deposition of the amyloid-beta peptide (Abeta)...
  42. Chapuis J, Vingtdeux V, Campagne F, Davies P, Marambaud P. Growth arrest-specific 1 binds to and controls the maturation and processing of the amyloid-beta precursor protein. Hum Mol Genet. 2011;20:2026-36 pubmed publisher
    ..deposition of amyloid-? (A?), a series of peptides derived from the processing of the amyloid-? precursor protein (APP)...
  43. Wagner T, Pietrzik C. The role of lipoprotein receptors on the physiological function of APP. Exp Brain Res. 2012;217:377-87 pubmed publisher
    ..low-density lipoprotein receptor (LDL-R) family that are involved in trafficking and processing of the amyloid precursor protein (APP)...
  44. Schmidt V, Baum K, Lao A, Rateitschak K, Schmitz Y, Teichmann A, et al. Quantitative modelling of amyloidogenic processing and its influence by SORLA in Alzheimer's disease. EMBO J. 2012;31:187-200 pubmed publisher
    The extent of proteolytic processing of the amyloid precursor protein (APP) into neurotoxic amyloid-? (A?) peptides is central to the pathology of Alzheimer's disease (AD)...
  45. Chen X, Stern D, Yan S. Mitochondrial dysfunction and Alzheimer's disease. Curr Alzheimer Res. 2006;3:515-20 pubmed
    ..accumulates in mitochndrial matrix, as demonstrated in both transgenic mice over-expressing mutant amyloid precursor protein (APP) and autopsy brain from AD patients...
  46. Chang K, Kim H, Ha T, Ha J, Shin K, Jeong Y, et al. Phosphorylation of amyloid precursor protein (APP) at Thr668 regulates the nuclear translocation of the APP intracellular domain and induces neurodegeneration. Mol Cell Biol. 2006;26:4327-38 pubmed
    b>Amyloid precursor protein (APP) has eight potential phosphorylation sites in its cytoplasmic domain...
  47. Xia W, Ray W, Ostaszewski B, Rahmati T, Kimberly W, Wolfe M, et al. Presenilin complexes with the C-terminal fragments of amyloid precursor protein at the sites of amyloid beta-protein generation. Proc Natl Acad Sci U S A. 2000;97:9299-304 pubmed
    An unusual intramembranous cleavage of the beta-amyloid precursor protein (APP) by gamma-secretase is the final step in the generation of amyloid beta-peptide (Abeta)...
  48. Saganich M, Schroeder B, Galvan V, Bredesen D, Koo E, Heinemann S. Deficits in synaptic transmission and learning in amyloid precursor protein (APP) transgenic mice require C-terminal cleavage of APP. J Neurosci. 2006;26:13428-36 pubmed
    ..Amyloid-beta protein (Abeta) is thought to play an important role in disease-related synaptic dysfunction, but the mechanism by which Abeta ..
  49. Ha S, Furukawa R, Fechheimer M. Association of AICD and Fe65 with Hirano bodies reduces transcriptional activation and initiation of apoptosis. Neurobiol Aging. 2011;32:2287-98 pubmed publisher
    ..Thus, association of AICD and Fe65 with Hirano bodies impedes their function in promoting apoptosis and modulating transcription. ..
  50. Obregon D, Hou H, Deng J, Giunta B, Tian J, Darlington D, et al. Soluble amyloid precursor protein-? modulates ?-secretase activity and amyloid-? generation. Nat Commun. 2012;3:777 pubmed publisher
    ..Here we show that soluble amyloid precursor protein-? (sAPP-?) decreases A? generation by directly associating with ?-site APP-converting enzyme (BACE)1, ..
  51. Nakagawa T, Yuan J. Cross-talk between two cysteine protease families. Activation of caspase-12 by calpain in apoptosis. J Cell Biol. 2000;150:887-94 pubmed
    ..These data suggest a novel apoptotic pathway involving calcium-mediated calpain activation and cross-talks between calpain and caspase families. ..
  52. Lahiri D, Ghosh C, Ge Y. A proximal gene promoter region for the beta-amyloid precursor protein provides a link between development, apoptosis, and Alzheimer's disease. Ann N Y Acad Sci. 2003;1010:643-7 pubmed
    Abnormalities in regulation of the beta-amyloid precursor protein (APP) gene might be a crucial factor in Alzheimer's disease (AD). Our aim is to study the role of a specific proximal APP promoter element under the apoptotic condition...
  53. Andersen O, Schmidt V, Spoelgen R, Gliemann J, Behlke J, Galatis D, et al. Molecular dissection of the interaction between amyloid precursor protein and its neuronal trafficking receptor SorLA/LR11. Biochemistry. 2006;45:2618-28 pubmed
    SorLA/LR11 is a sorting receptor that regulates the intracellular transport and processing of the amyloid precursor protein (APP) in neurons...
  54. Grant M, Lazo N, Lomakin A, Condron M, Arai H, Yamin G, et al. Familial Alzheimer's disease mutations alter the stability of the amyloid beta-protein monomer folding nucleus. Proc Natl Acad Sci U S A. 2007;104:16522-7 pubmed
    Amyloid beta-protein (Abeta) oligomers may be the proximate neurotoxins in Alzheimer's disease (AD)...
  55. Yoshimoto M, Iwai A, Kang D, Otero D, Xia Y, Saitoh T. NACP, the precursor protein of the non-amyloid beta/A4 protein (A beta) component of Alzheimer disease amyloid, binds A beta and stimulates A beta aggregation. Proc Natl Acad Sci U S A. 1995;92:9141-5 pubmed
    ..Thus, NACP can bind A beta peptides through the specific sequence and can promote A beta aggregation, raising the possibility that NACP may play a role in the development of AD amyloid. ..
  56. Iijima K, Ando K, Takeda S, Satoh Y, Seki T, Itohara S, et al. Neuron-specific phosphorylation of Alzheimer's beta-amyloid precursor protein by cyclin-dependent kinase 5. J Neurochem. 2000;75:1085-91 pubmed
    The mature form of Alzheimer's beta-amyloid precursor protein (APP) is phosphorylated specifically at Thr(668) in neurons...
  57. Ando K, Iijima K, Elliott J, Kirino Y, Suzuki T. Phosphorylation-dependent regulation of the interaction of amyloid precursor protein with Fe65 affects the production of beta-amyloid. J Biol Chem. 2001;276:40353-61 pubmed
    Neuronal Fe65 is an adapter protein that interacts with the cytoplasmic domain of the beta-amyloid precursor protein (APP)...
  58. Lee M, You H, Cho S, Woo C, Yoo M, Joe E, et al. Implication of the small GTPase Rac1 in the generation of reactive oxygen species in response to beta-amyloid in C6 astroglioma cells. Biochem J. 2002;366:937-43 pubmed
    Exogenous application of beta-amyloid (Abeta(25-35), a fragment of Abeta(1-42)) significantly elevated levels of reactive oxygen species (ROS) in C6 astroglioma cells, as measured by confocal microscopic analysis of H(2)O(2)-sensitive 2',..
  59. Kakio A, Nishimoto S, Kozutsumi Y, Matsuzaki K. Formation of a membrane-active form of amyloid beta-protein in raft-like model membranes. Biochem Biophys Res Commun. 2003;303:514-8 pubmed
    ..These results suggest that the lipid raft containing a ganglioside cluster serves as a conformational catalyst or a chaperon generating a membrane-active form of A beta with seeding ability. ..
  60. Allinson T, Parkin E, Condon T, Schwager S, Sturrock E, Turner A, et al. The role of ADAM10 and ADAM17 in the ectodomain shedding of angiotensin converting enzyme and the amyloid precursor protein. Eur J Biochem. 2004;271:2539-47 pubmed
    ..including the blood pressure regulating angiotensin converting enzyme (ACE) and the Alzheimer's disease amyloid precursor protein (APP), are proteolytically shed from the plasma membrane by metalloproteases...
  61. Du H, Guo L, Fang F, Chen D, Sosunov A, McKhann G, et al. Cyclophilin D deficiency attenuates mitochondrial and neuronal perturbation and ameliorates learning and memory in Alzheimer's disease. Nat Med. 2008;14:1097-105 pubmed publisher
    ..Here we show that interaction of CypD with mitochondrial amyloid-beta protein (Abeta) potentiates mitochondrial, neuronal and synaptic stress...
  62. Lahiri D, Maloney B. Beyond the signaling effect role of amyloid-ß42 on the processing of APP, and its clinical implications. Exp Neurol. 2010;225:51-4 pubmed publisher
    ..Basic understanding of the activities of the amyloid beta peptide (Abeta) and associated proteins such as beta-site APP-cleaving enzyme 1 (BACE1) is necessary to develop effective medical ..
  63. Treusch S, Hamamichi S, Goodman J, Matlack K, Chung C, Baru V, et al. Functional links between A? toxicity, endocytic trafficking, and Alzheimer's disease risk factors in yeast. Science. 2011;334:1241-5 pubmed publisher
    ..Thus, links between A?, endocytosis, and human AD risk factors can be ascertained with yeast as a model system. ..
  64. Herskowitz J, Offe K, Deshpande A, Kahn R, Levey A, Lah J. GGA1-mediated endocytic traffic of LR11/SorLA alters APP intracellular distribution and amyloid-? production. Mol Biol Cell. 2012;23:2645-57 pubmed publisher
    Proteolytic processing of the amyloid-? precursor protein (APP) and generation of amyloid-? peptide (A?) are key events in Alzheimer's disease (AD) pathogenesis...
  65. Long J, Lahiri D. MicroRNA-101 downregulates Alzheimer's amyloid-? precursor protein levels in human cell cultures and is differentially expressed. Biochem Biophys Res Commun. 2011;404:889-95 pubmed publisher
    ..repertoire of regulatory interactions utilized by human cells to control expression of amyloid-? precursor protein (APP) is still undefined. We investigated here the contribution of microRNA (miRNA) to this regulatory network...
  66. Khvotchev M, Sudhof T. Proteolytic processing of amyloid-beta precursor protein by secretases does not require cell surface transport. J Biol Chem. 2004;279:47101-8 pubmed
    ..protein (APP) by alpha-,beta-, and gamma-secretases releases an extracellular fragment called APPS, small Abeta peptides, and a short APP intracellular domain that may provide a transcriptional signal analogous to the Notch ..
  67. Gylys K, Fein J, Yang F, Wiley D, Miller C, Cole G. Synaptic changes in Alzheimer's disease: increased amyloid-beta and gliosis in surviving terminals is accompanied by decreased PSD-95 fluorescence. Am J Pathol. 2004;165:1809-17 pubmed
  68. Lockhart A, Ye L, Judd D, Merritt A, Lowe P, Morgenstern J, et al. Evidence for the presence of three distinct binding sites for the thioflavin T class of Alzheimer's disease PET imaging agents on beta-amyloid peptide fibrils. J Biol Chem. 2005;280:7677-84 pubmed
    ..and a wide range of ligands are currently under development for the detection of beta-amyloid peptide (Abeta)-containing plaques by using positron emission tomography...
  69. Belyaev N, Kellett K, Beckett C, Makova N, Revett T, Nalivaeva N, et al. The transcriptionally active amyloid precursor protein (APP) intracellular domain is preferentially produced from the 695 isoform of APP in a {beta}-secretase-dependent pathway. J Biol Chem. 2010;285:41443-54 pubmed publisher
    Amyloidogenic processing of the amyloid precursor protein (APP) by ?- and ?-secretases generates several biologically active products, including amyloid-? (A?) and the APP intracellular domain (AICD)...
  70. Bullido M, Munoz Fernandez M, Recuero M, Fresno M, Valdivieso F. Alzheimer's amyloid precursor protein is expressed on the surface of hematopoietic cells upon activation. Biochim Biophys Acta. 1996;1313:54-62 pubmed
    ..This 39-42 amino acid peptide is derived from a larger precursor protein (APP)...
  71. Tamboli I, Prager K, Barth E, Heneka M, Sandhoff K, Walter J. Inhibition of glycosphingolipid biosynthesis reduces secretion of the beta-amyloid precursor protein and amyloid beta-peptide. J Biol Chem. 2005;280:28110-7 pubmed
    ..Amyloid beta-peptides are generated by proteolytic processing of the beta-amyloid precursor protein by beta- and gamma-secretases...
  72. Jesudason E, Masilamoni J, Ashok B, Baben B, Arul V, Jesudoss K, et al. Inhibitory effects of short-term administration of DL-alpha-lipoic acid on oxidative vulnerability induced by Abeta amyloid fibrils (25-35) in mice. Mol Cell Biochem. 2008;311:145-56 pubmed publisher
    b>Abeta amyloid peptide is believed to induce oxidative stress leading to inflammation, which is postulated to play a significant role in the toxicity of Alzheimer's disease (AD)...
  73. Mawuenyega K, Sigurdson W, Ovod V, Munsell L, Kasten T, Morris J, et al. Decreased clearance of CNS beta-amyloid in Alzheimer's disease. Science. 2010;330:1774 pubmed publisher
    ..On average, there were no differences in A?40 or A?42 production rates. Thus, the common late-onset form of Alzheimer's disease is characterized by an overall impairment in A? clearance. ..
  74. Choy R, Cheng Z, Schekman R. Amyloid precursor protein (APP) traffics from the cell surface via endosomes for amyloid ? (A?) production in the trans-Golgi network. Proc Natl Acad Sci U S A. 2012;109:E2077-82 pubmed publisher
    b>Amyloid precursor protein (APP) is processed sequentially by the ?-site APP cleaving enzyme and ?-secretase to generate amyloid ? (A?) peptides, one of the hallmarks of Alzheimer's disease...
  75. Dahms S, Könnig I, Roeser D, Gührs K, Mayer M, Kaden D, et al. Metal binding dictates conformation and function of the amyloid precursor protein (APP) E2 domain. J Mol Biol. 2012;416:438-52 pubmed publisher
    The amyloid precursor protein (APP) and its neurotoxic cleavage product A? are key players in the development of Alzheimer's disease and appear essential for neuronal development and cell homeostasis in mammals...
  76. Tanzi R, McClatchey A, Lamperti E, Villa Komaroff L, Gusella J, Neve R. Protease inhibitor domain encoded by an amyloid protein precursor mRNA associated with Alzheimer's disease. Nature. 1988;331:528-30 pubmed
    ..The amyloid protein precursor (APP) gene is expressed in brain and in several peripheral tissues, but the specific biochemical events leading to ..
  77. Buxbaum J, Liu K, Luo Y, Slack J, Stocking K, Peschon J, et al. Evidence that tumor necrosis factor alpha converting enzyme is involved in regulated alpha-secretase cleavage of the Alzheimer amyloid protein precursor. J Biol Chem. 1998;273:27765-7 pubmed
    The amyloid protein, Abeta, which accumulates in the brains of Alzheimer patients, is derived by proteolysis of the amyloid protein precursor (APP)...
  78. Oppermann U, Salim S, Tjernberg L, Terenius L, Jornvall H. Binding of amyloid beta-peptide to mitochondrial hydroxyacyl-CoA dehydrogenase (ERAB): regulation of an SDR enzyme activity with implications for apoptosis in Alzheimer's disease. FEBS Lett. 1999;451:238-42 pubmed
    ..The interaction of A beta with ERAB further links oxidoreductase activity with both apoptosis and amyloid toxicity. ..
  79. Hartley D, Zhao C, Speier A, Woodard G, Li S, Li Z, et al. Transglutaminase induces protofibril-like amyloid beta-protein assemblies that are protease-resistant and inhibit long-term potentiation. J Biol Chem. 2008;283:16790-800 pubmed publisher
    An increasing body of evidence suggests that soluble assemblies of amyloid beta-protein (Abeta) play an important role in the initiation of Alzheimer disease (AD)...
  80. Kumar Singh S, De Jonghe C, Cruts M, Kleinert R, Wang R, Mercken M, et al. Nonfibrillar diffuse amyloid deposition due to a gamma(42)-secretase site mutation points to an essential role for N-truncated A beta(42) in Alzheimer's disease. Hum Mol Genet. 2000;9:2589-98 pubmed
    Amyloidogenic processing of the amyloid precursor protein (APP) with deposition in brain of the 42 amino acid long amyloid beta-peptide (A beta(42)) is considered central to Alzheimer's disease (AD) pathology...
  81. Schmitz A, Schneider A, Kummer M, Herzog V. Endoplasmic reticulum-localized amyloid beta-peptide is degraded in the cytosol by two distinct degradation pathways. Traffic. 2004;5:89-101 pubmed
    ..Analyzing the degradation of ER-localized amyloid beta-peptide (Abeta), we found a divergence from this general model...
  82. Petkova A, Leapman R, Guo Z, Yau W, Mattson M, Tycko R. Self-propagating, molecular-level polymorphism in Alzheimer's beta-amyloid fibrils. Science. 2005;307:262-5 pubmed
    ..magnetic resonance measurements on fibrils formed by the 40-residue beta-amyloid peptide of Alzheimer's disease (Abeta(1-40)), we show that different fibril morphologies have different underlying molecular structures, that the ..
  83. Ghidoni R, Albertini V, Squitti R, Paterlini A, Bruno A, Bernardini S, et al. Novel T719P AbetaPP mutation unbalances the relative proportion of amyloid-beta peptides. J Alzheimers Dis. 2009;18:295-303 pubmed publisher
    ..desorption/ionization mass spectrometry (SELDI-TOF MS), we determined mass profiles of amyloid-beta peptides (Abeta) in cerebrospinal fluid (CSF) of the AbetaPP mutated patient, healthy control subjects (n = 10), and of two ..
  84. Kamino K, Orr H, Payami H, Wijsman E, Alonso M, Pulst S, et al. Linkage and mutational analysis of familial Alzheimer disease kindreds for the APP gene region. Am J Hum Genet. 1992;51:998-1014 pubmed
    ..number of familial Alzheimer disease (FAD) kindreds were examined to determine whether mutations in the amyloid precursor protein (APP) gene could be responsible for the disease...
  85. Tomita S, Ozaki T, Taru H, Oguchi S, Takeda S, Yagi Y, et al. Interaction of a neuron-specific protein containing PDZ domains with Alzheimer's amyloid precursor protein. J Biol Chem. 1999;274:2243-54 pubmed
    ..X11L interacts with a sequence containing the NPXY motif found in the cytoplasmic domain of Alzheimer's amyloid precursor protein. A construct lacking the carboxyl-terminal domain, which comprises two PDZ domains (N + PI), enhances PI ..
  86. Buchhave P, Minthon L, Zetterberg H, Wallin A, Blennow K, Hansson O. Cerebrospinal fluid levels of ?-amyloid 1-42, but not of tau, are fully changed already 5 to 10 years before the onset of Alzheimer dementia. Arch Gen Psychiatry. 2012;69:98-106 pubmed publisher
    ..These results provide direct support in humans for the hypothesis that altered A? metabolism precedes tau-related pathology and neuronal degeneration. ..
  87. Oltersdorf T, Fritz L, Schenk D, Lieberburg I, Johnson Wood K, Beattie E, et al. The secreted form of the Alzheimer's amyloid precursor protein with the Kunitz domain is protease nexin-II. Nature. 1989;341:144-7 pubmed
    ..neuritic plaques in Alzheimer's disease and is derived from a membrane-bound amyloid protein precursor (APP)...
  88. Kanekiyo T, Liu C, Shinohara M, Li J, Bu G. LRP1 in brain vascular smooth muscle cells mediates local clearance of Alzheimer's amyloid-?. J Neurosci. 2012;32:16458-65 pubmed publisher
    ..Conditional deletion of Lrp1 in vascular smooth muscle cell in amyloid model APP/PS1 mice accelerated brain A? accumulation and exacerbated A? deposition as amyloid plaques and CAA without ..