CoChat
Sign Up
Cited by 983Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

APP processing in Alzheimer’s disease.

Open access
Zhang, Yun-wu, Thompson, Robert, Zhang, Han, Xu, Huaxi·2011·Molecular Brain
DOI 10.1186/1756-6606-4-3PMC PMC3022812
Open this paper in CoChat — free accountOpen PDF

Abstract

An important pathological feature of Alzheimer's disease (AD) is the presence of extracellular senile plaques in the brain. Senile plaques are composed of aggregations of small peptides called β-amyloid (Aβ). Multiple lines of evidence demonstrate that overproduction/aggregation of Aβ in the brain is a primary cause of AD and inhibition of Aβ generation has become a hot topic in AD research. Aβ is generated from β-amyloid precursor protein (APP) through sequential cleavages first by β-secretase and then by γ-secretase complex. Alternatively, APP can be cleaved by α-secretase within the Aβ domain to release soluble APPα and preclude Aβ generation. Cleavage of APP by caspases may also contribute to AD pathologies. Therefore, understanding the metabolism/processing of APP is crucial for AD therapeutics. Here we review current knowledge of APP processing regulation as well as the patho/physiological functions of APP and its metabolites.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1186/1756-6606-4-3

Cites

22 of 22 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • BACE1 cleavage of APP is the rate-limiting step along the amyloidogenic processing pathway.

    “BACE1 cleavage of APP is the rate-limiting step along the amyloidogenic processing pathway (Thinakaran and Koo, 2008; Zhang et al., 2011)”

    From Distinct anterograde trafficking pathways of BACE1 and amyloid precursor protein from the TGN and the regulation of amyloid-β production (2020) · cites this paper as Zhang et al., 2011

    In Background > APP Processing, the paper identifies BACE1 cleavage as the first step in Aβ generation and says BACE1 activity is thought to be rate-limiting. The citing sentence presents that qualified assessment as an established fact. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Increased Aβ production can contribute substantially to extracellular Aβ accumulation and the amyloid cascade underlying Alzheimer's disease pathology, but impaired turnover and clearance can also promote Aβ accumulation.

    “Increased Aβ production can contribute substantially to extracellular Aβ accumulation and the amyloid cascade underlying Alzheimer’s disease pathology (Chow et al., 2010; Zhang et al., 2011) but impaired turnover and clearance can also promote Aβ accumulation.”

    From Isogenic human stem cell models reveal mutation-dependent protective mechanisms of APOE3 Christchurch (2026) · cites this paper as Zhang et al., 2011

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 190

  1. Sherrington R Rogaev EI Liang Y Rogaeva EA Levesque G Ikeda M Chi H Lin C Li G Holman K Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease Nature 1995 375 754 760 10.1038/375754a0 7596406 · DOI · Paper page
  2. Goate A Chartier-Harlin MC Mullan M Brown J Crawford F Fidani L Giuffra L Haynes A Irving N James L Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease Nature 1991 349 704 706 10.1038/349704a0 1671712 · DOI · Paper page
  3. Buee L Bussiere T Buee-Scherrer V Delacourte A Hof PR Tau protein isoforms, phosphorylation and role in neurodegenerative disorders Brain Res Brain Res Rev 2000 33 95 130 10.1016/S0165-0173(00)00019-9 10967355 · DOI
  4. Gendron TF Petrucelli L The role of tau in neurodegeneration Mol Neurodegener 2009 4 13 10.1186/1750-1326-4-13 19284597 PMC2663562 · DOI · Paper page
  5. Selkoe DJ The cell biology of beta-amyloid precursor protein and presenilin in Alzheimer's disease Trends Cell Biol 1998 8 447 453 10.1016/S0962-8924(98)01363-4 9854312 · DOI · Paper page
  6. Rohan de Silva HA Jen A Wickenden C Jen LS Wilkinson SL Patel AJ Cell-specific expression of beta-amyloid precursor protein isoform mRNAs and proteins in neurons and astrocytes Brain Res Mol Brain Res 1997 47 147 156 10.1016/S0169-328X(97)00045-4 9221912 · DOI
  7. Kang J Muller-Hill B Differential splicing of Alzheimer's disease amyloid A4 precursor RNA in rat tissues: PreA4(695) mRNA is predominantly produced in rat and human brain Biochem Biophys Res Commun 1990 166 1192 1200 10.1016/0006-291X(90)90992-V 1689572 · DOI
  8. Menendez-Gonzalez M Perez-Pinera P Martinez-Rivera M Calatayud MT Blazquez Menes B APP processing and the APP-KPI domain involvement in the amyloid cascade Neurodegener Dis 2005 2 277 283 10.1159/000092315 16909010 · DOI
  9. Bordji K Becerril-Ortega J Nicole O Buisson A Activation of extrasynaptic, but not synaptic, NMDA receptors modifies amyloid precursor protein expression pattern and increases amyloid-ss production J Neurosci 2010 30 15927 15942 10.1523/JNEUROSCI.3021-10.2010 21106831 PMC6633754 · DOI
  10. Wasco W Bupp K Magendantz M Gusella JF Tanzi RE Solomon F Identification of a mouse brain cDNA that encodes a protein related to the Alzheimer disease-associated amyloid beta protein precursor Proc Natl Acad Sci USA 1992 89 10758 10762 10.1073/pnas.89.22.10758 1279693 PMC50421 · DOI
  11. Wasco W Gurubhagavatula S Paradis MD Romano DM Sisodia SS Hyman BT Neve RL Tanzi RE Isolation and characterization of APLP2 encoding a homologue of the Alzheimer's associated amyloid beta protein precursor Nat Genet 1993 5 95 100 10.1038/ng0993-95 8220435 · DOI
  12. Coulson EJ Paliga K Beyreuther K Masters CL What the evolution of the amyloid protein precursor supergene family tells us about its function Neurochem Int 2000 36 175 184 10.1016/S0197-0186(99)00125-4 10676850 · DOI
  13. Zheng H Jiang M Trumbauer ME Sirinathsinghji DJ Hopkins R Smith DW Heavens RP Dawson GR Boyce S Conner MW beta-Amyloid precursor protein-deficient mice show reactive gliosis and decreased locomotor activity Cell 1995 81 525 531 10.1016/0092-8674(95)90073-X 7758106 · DOI
  14. Dawson GR Seabrook GR Zheng H Smith DW Graham S O'Dowd G Bowery BJ Boyce S Trumbauer ME Chen HY Age-related cognitive deficits, impaired long-term potentiation and reduction in synaptic marker density in mice lacking the beta-amyloid precursor protein Neuroscience 1999 90 1 13 10.1016/S0306-4522(98)00410-2 10188929 · DOI
  15. von Koch CS Zheng H Chen H Trumbauer M Thinakaran G van der Ploeg LH Price DL Sisodia SS Generation of APLP2 KO mice and early postnatal lethality in APLP2/APP double KO mice Neurobiol Aging 1997 18 661 669 10.1016/S0197-4580(97)00151-6 9461064 · DOI
  16. Heber S Herms J Gajic V Hainfellner J Aguzzi A Rulicke T von Kretzschmar H von Koch C Sisodia S Tremml P Mice with combined gene knock-outs reveal essential and partially redundant functions of amyloid precursor protein family members J Neurosci 2000 20 7951 7963 11050115 PMC6772747
  17. Herms J Anliker B Heber S Ring S Fuhrmann M Kretzschmar H Sisodia S Muller U Cortical dysplasia resembling human type 2 lissencephaly in mice lacking all three APP family members Embo J 2004 23 4106 4115 10.1038/sj.emboj.7600390 15385965 PMC524337 · DOI
  18. Zheng H Koo EH The amyloid precursor protein: beyond amyloid Mol Neurodegener 2006 1 5 10.1186/1750-1326-1-5 16930452 PMC1538601 · DOI
  19. Ho A Sudhof TC Binding of F-spondin to amyloid-beta precursor protein: a candidate amyloid-beta precursor protein ligand that modulates amyloid-beta precursor protein cleavage Proc Natl Acad Sci USA 2004 101 2548 2553 10.1073/pnas.0308655100 14983046 PMC356987 · DOI · Paper page
  20. Lourenco FC Galvan V Fombonne J Corset V Llambi F Muller U Bredesen DE Mehlen P Netrin-1 interacts with amyloid precursor protein and regulates amyloid-beta production Cell Death Differ 2009 16 655 663 10.1038/cdd.2008.191 19148186 PMC2757418 · DOI
  21. Yamazaki T Koo EH Selkoe DJ Cell surface amyloid beta-protein precursor colocalizes with beta 1 integrins at substrate contact sites in neural cells J Neurosci 1997 17 1004 1010 8994055 PMC6573178
  22. Wang Y Ha Y The X-ray structure of an antiparallel dimer of the human amyloid precursor protein E2 domain Mol Cell 2004 15 343 353 10.1016/j.molcel.2004.06.037 15304215 · DOI
  23. Soba P Eggert S Wagner K Zentgraf H Siehl K Kreger S Lower A Langer A Merdes G Paro R Homo- and heterodimerization of APP family members promotes intercellular adhesion Embo J 2005 24 3624 3634 10.1038/sj.emboj.7600824 16193067 PMC1276707 · DOI
  24. Kamal A Stokin GB Yang Z Xia CH Goldstein LS Axonal transport of amyloid precursor protein is mediated by direct binding to the kinesin light chain subunit of kinesin-I Neuron 2000 28 449 459 10.1016/S0896-6273(00)00124-0 11144355 · DOI · Paper page
  25. Kamal A Almenar-Queralt A LeBlanc JF Roberts EA Goldstein LS Kinesin-mediated axonal transport of a membrane compartment containing beta-secretase and presenilin-1 requires APP Nature 2001 414 643 648 10.1038/414643a 11740561 · DOI · Paper page
  26. Lazarov O Morfini GA Lee EB Farah MH Szodorai A DeBoer SR Koliatsos VE Kins S Lee VM Wong PC Axonal transport, amyloid precursor protein, kinesin-1, and the processing apparatus: revisited J Neurosci 2005 25 2386 2395 10.1523/JNEUROSCI.3089-04.2005 15745965 PMC6726084 · DOI
  27. Liu Y Zhang YW Wang X Zhang H You X Liao FF Xu H Intracellular trafficking of presenilin 1 is regulated by beta-amyloid precursor protein and phospholipase D1 J Biol Chem 2009 284 12145 12152 10.1074/jbc.M808497200 19276086 PMC2673283 · DOI
  28. Satpute-Krishnan P DeGiorgis JA Bearer EL Fast anterograde transport of herpes simplex virus: role for the amyloid precursor protein of alzheimer's disease Aging Cell 2003 2 305 318 10.1046/j.1474-9728.2003.00069.x 14677633 PMC3622731 · DOI
  29. Satpute-Krishnan P DeGiorgis JA Conley MP Jang M Bearer EL A peptide zipcode sufficient for anterograde transport within amyloid precursor protein Proc Natl Acad Sci USA 2006 103 16532 16537 10.1073/pnas.0607527103 17062754 PMC1621108 · DOI
  30. Wang B Yang L Wang Z Zheng H Amyolid precursor protein mediates presynaptic localization and activity of the high-affinity choline transporter Proc Natl Acad Sci USA 2007 104 14140 14145 10.1073/pnas.0704070104 17709753 PMC1955810 · DOI
  31. Xu H Sweeney D Wang R Thinakaran G Lo AC Sisodia SS Greengard P Gandy S Generation of Alzheimer beta-amyloid protein in the trans-Golgi network in the apparent absence of vesicle formation Proc Natl Acad Sci USA 1997 94 3748 3752 10.1073/pnas.94.8.3748 9108049 PMC20512 · DOI
  32. Hartmann T Bieger SC Bruhl B Tienari PJ Ida N Allsop D Roberts GW Masters CL Dotti CG Unsicker K Distinct sites of intracellular production for Alzheimer's disease A beta40/42 amyloid peptides Nat Med 1997 3 1016 1020 10.1038/nm0997-1016 9288729 · DOI
  33. Greenfield JP Tsai J Gouras GK Hai B Thinakaran G Checler F Sisodia SS Greengard P Xu H Endoplasmic reticulum and trans-Golgi network generate distinct populations of Alzheimer beta-amyloid peptides Proc Natl Acad Sci USA 1999 96 742 747 10.1073/pnas.96.2.742 9892704 PMC15207 · DOI · Paper page
  34. Sisodia SS Beta-amyloid precursor protein cleavage by a membrane-bound protease Proc Natl Acad Sci USA 1992 89 6075 6079 10.1073/pnas.89.13.6075 1631093 PMC49440 · DOI
  35. Nordstedt C Caporaso GL Thyberg J Gandy SE Greengard P Identification of the Alzheimer beta/A4 amyloid precursor protein in clathrin-coated vesicles purified from PC12 cells J Biol Chem 1993 268 608 612 8416966
  36. Caporaso GL Takei K Gandy SE Matteoli M Mundigl O Greengard P De Camilli P Morphologic and biochemical analysis of the intracellular trafficking of the Alzheimer beta/A4 amyloid precursor protein J Neurosci 1994 14 3122 3138 8182461 PMC6577440
  37. Haass C Hung AY Schlossmacher MG Teplow DB Selkoe DJ beta-Amyloid peptide and a 3-kDa fragment are derived by distinct cellular mechanisms J Biol Chem 1993 268 3021 3024 8428976
  38. Haass C Hung AY Schlossmacher MG Oltersdorf T Teplow DB Selkoe DJ Normal cellular processing of the beta-amyloid precursor protein results in the secretion of the amyloid beta peptide and related molecules Ann N Y Acad Sci 1993 695 109 116 10.1111/j.1749-6632.1993.tb23037.x 8239267 · DOI
  39. Furukawa K Sopher BL Rydel RE Begley JG Pham DG Martin GM Fox M Mattson MP Increased activity-regulating and neuroprotective efficacy of alpha-secretase-derived secreted amyloid precursor protein conferred by a C-terminal heparin-binding domain J Neurochem 1996 67 1882 1896 10.1046/j.1471-4159.1996.67051882.x 8863493 · DOI
  40. Han P Dou F Li F Zhang X Zhang YW Zheng H Lipton SA Xu H Liao FF Suppression of cyclin-dependent kinase 5 activation by amyloid precursor protein: a novel excitoprotective mechanism involving modulation of tau phosphorylation J Neurosci 2005 25 11542 11552 10.1523/JNEUROSCI.3831-05.2005 16354912 PMC6726015 · DOI
  41. Roberts SB Ripellino JA Ingalls KM Robakis NK Felsenstein KM Non-amyloidogenic cleavage of the beta-amyloid precursor protein by an integral membrane metalloendopeptidase J Biol Chem 1994 269 3111 3116 8300647
  42. Buxbaum JD Liu KN Luo Y Slack JL Stocking KL Peschon JJ Johnson RS Castner BJ Cerretti DP Black RA 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 27767 10.1074/jbc.273.43.27765 9774383 · DOI
  43. Blacker M Noe MC Carty TJ Goodyer CG LeBlanc AC Effect of tumor necrosis factor-alpha converting enzyme (TACE) and metalloprotease inhibitor on amyloid precursor protein metabolism in human neurons J Neurochem 2002 83 1349 1357 10.1046/j.1471-4159.2002.01228.x 12472889 · DOI
  44. Merlos-Suarez A Ruiz-Paz S Baselga J Arribas J Metalloprotease-dependent protransforming growth factor-alpha ectodomain shedding in the absence of tumor necrosis factor-alpha-converting enzyme J Biol Chem 2001 276 48510 48517 11600492
  45. Koike H Tomioka S Sorimachi H Saido TC Maruyama K Okuyama A Fujisawa-Sehara A Ohno S Suzuki K Ishiura S Membrane-anchored metalloprotease MDC9 has an alpha-secretase activity responsible for processing the amyloid precursor protein Biochem J 1999 343 Pt 2 371 375 10.1042/0264-6021:3430371 10510302 PMC1220563 · DOI
  46. Lopez-Perez E Zhang Y Frank SJ Creemers J Seidah N Checler F Constitutive alpha-secretase cleavage of the beta-amyloid precursor protein in the furin-deficient LoVo cell line: involvement of the pro-hormone convertase 7 and the disintegrin metalloprotease ADAM10 J Neurochem 2001 76 1532 1539 10.1046/j.1471-4159.2001.00180.x 11238737 · DOI
  47. Lammich S Kojro E Postina R Gilbert S Pfeiffer R Jasionowski M Haass C Fahrenholz F Constitutive and regulated alpha-secretase cleavage of Alzheimer's amyloid precursor protein by a disintegrin metalloprotease Proc Natl Acad Sci USA 1999 96 3922 3927 10.1073/pnas.96.7.3922 10097139 PMC22396 · DOI
  48. Jorissen E Prox J Bernreuther C Weber S Schwanbeck R Serneels L Snellinx A Craessaerts K Thathiah A Tesseur I The disintegrin/metalloproteinase ADAM10 is essential for the establishment of the brain cortex J Neurosci 2010 30 4833 4844 10.1523/JNEUROSCI.5221-09.2010 20371803 PMC2921981 · DOI · Paper page
  49. Colciaghi F Borroni B Pastorino L Marcello E Zimmermann M Cattabeni F Padovani A Di Luca M [alpha]-Secretase ADAM10 as well as [alpha]APPs is reduced in platelets and CSF of Alzheimer disease patients Mol Med 2002 8 67 74 12080182 PMC2039975
  50. Tyler SJ Dawbarn D Wilcock GK Allen SJ alpha- and beta-secretase: profound changes in Alzheimer's disease Biochem Biophys Res Commun 2002 299 373 376 10.1016/S0006-291X(02)02635-9 12445809 · DOI
  51. Caille I Allinquant B Dupont E Bouillot C Langer A Muller U Prochiantz A Soluble form of amyloid precursor protein regulates proliferation of progenitors in the adult subventricular zone Development 2004 131 2173 2181 10.1242/dev.01103 15073156 · DOI
  52. Ohsawa I Takamura C Morimoto T Ishiguro M Kohsaka S Amino-terminal region of secreted form of amyloid precursor protein stimulates proliferation of neural stem cells Eur J Neurosci 1999 11 1907 1913 10.1046/j.1460-9568.1999.00601.x 10336659 · DOI
  53. Ma T Zhao Y Kwak YD Yang Z Thompson R Luo Z Xu H Liao FF Statin's excitoprotection is mediated by sAPP and the subsequent attenuation of calpain-induced truncation events, likely via rho-ROCK signaling J Neurosci 2009 29 11226 11236 10.1523/JNEUROSCI.6150-08.2009 19741129 PMC2757921 · DOI
  54. Marcade M Bourdin J Loiseau N Peillon H Rayer A Drouin D Schweighoffer F Desire L Etazolate, a neuroprotective drug linking GABA(A) receptor pharmacology to amyloid precursor protein processing J Neurochem 2008 106 392 404 10.1111/j.1471-4159.2008.05396.x 18397369 · DOI
  55. Levites Y Amit T Mandel S Youdim MB Neuroprotection and neurorescue against Abeta toxicity and PKC-dependent release of nonamyloidogenic soluble precursor protein by green tea polyphenol (-)-epigallocatechin-3-gallate Faseb J 2003 17 952 954 12670874
  56. Ring S Weyer SW Kilian SB Waldron E Pietrzik CU Filippov MA Herms J Buchholz C Eckman CB Korte M The secreted beta-amyloid precursor protein ectodomain APPs alpha is sufficient to rescue the anatomical, behavioral, and electrophysiological abnormalities of APP-deficient mice J Neurosci 2007 27 7817 7826 10.1523/JNEUROSCI.1026-07.2007 17634375 PMC6672885 · DOI · Paper page
  57. Sinha S Anderson JP Barbour R Basi GS Caccavello R Davis D Doan M Dovey HF Frigon N Hong J Purification and cloning of amyloid precursor protein beta-secretase from human brain Nature 1999 402 537 540 10.1038/990114 10591214 · DOI · Paper page
  58. Yan R Bienkowski MJ Shuck ME Miao H Tory MC Pauley AM Brashier JR Stratman NC Mathews WR Buhl AE Membrane-anchored aspartyl protease with Alzheimer's disease beta-secretase activity Nature 1999 402 533 537 10.1038/990107 10591213 · DOI · Paper page
  59. Lau KF McLoughlin DM Standen C Miller CC X11 alpha and x11 beta interact with presenilin-1 via their PDZ domains Mol Cell Neurosci 2000 16 557 565 10.1006/mcne.2000.0898 11083918 · DOI
  60. Cai H Wang Y McCarthy D Wen H Borchelt DR Price DL Wong PC BACE1 is the major beta-secretase for generation of Abeta peptides by neurons Nat Neurosci 2001 4 233 234 10.1038/85064 11224536 · DOI
  61. Creemers JW Ines Dominguez D Plets E Serneels L Taylor NA Multhaup G Craessaerts K Annaert W De Strooper B Processing of beta-secretase by furin and other members of the proprotein convertase family J Biol Chem 2001 276 4211 4217 10.1074/jbc.M006947200 11071887 · DOI
  62. Bennett BD Denis P Haniu M Teplow DB Kahn S Louis JC Citron M Vassar R A furin-like convertase mediates propeptide cleavage of BACE, the Alzheimer's beta-secretase J Biol Chem 2000 275 37712 37717 10.1074/jbc.M005339200 10956649 · DOI
  63. Walter J Fluhrer R Hartung B Willem M Kaether C Capell A Lammich S Multhaup G Haass C Phosphorylation regulates intracellular trafficking of beta-secretase J Biol Chem 2001 276 14634 14641 10.1074/jbc.M011116200 11278841 · DOI
  64. Huse JT Pijak DS Leslie GJ Lee VM Doms RW Maturation and endosomal targeting of beta-site amyloid precursor protein-cleaving enzyme. The Alzheimer's disease beta-secretase J Biol Chem 2000 275 33729 33737 10.1074/jbc.M004175200 10924510 · DOI · Paper page
  65. Huse JT Liu K Pijak DS Carlin D Lee VM Doms RW Beta-secretase processing in the trans-Golgi network preferentially generates truncated amyloid species that accumulate in Alzheimer's disease brain J Biol Chem 2002 277 16278 16284 10.1074/jbc.M111141200 11847218 · DOI
  66. He W Lu Y Qahwash I Hu XY Chang A Yan R Reticulon family members modulate BACE1 activity and amyloid-beta peptide generation Nat Med 2004 10 959 965 10.1038/nm1088 15286784 · DOI
  67. Murayama KS Kametani F Saito S Kume H Akiyama H Araki W Reticulons RTN3 and RTN4-B/C interact with BACE1 and inhibit its ability to produce amyloid beta-protein Eur J Neurosci 2006 24 1237 1244 10.1111/j.1460-9568.2006.05005.x 16965550 · DOI
  68. Shi Q Prior M He W Tang X Hu X Yan R Reduced amyloid deposition in mice overexpressing RTN3 is adversely affected by preformed dystrophic neurites J Neurosci 2009 29 9163 9173 10.1523/JNEUROSCI.5741-08.2009 19625507 PMC2743151 · DOI
  69. He X Li F Chang WP Tang J GGA proteins mediate the recycling pathway of memapsin 2 (BACE) J Biol Chem 2005 280 11696 11703 10.1074/jbc.M411296200 15615712 · DOI
  70. Tesco G Koh YH Kang EL Cameron AN Das S Sena-Esteves M Hiltunen M Yang SH Zhong Z Shen Y Depletion of GGA3 stabilizes BACE and enhances beta-secretase activity Neuron 2007 54 721 737 10.1016/j.neuron.2007.05.012 17553422 PMC1973166 · DOI · Paper page
  71. Wahle T Prager K Raffler N Haass C Famulok M Walter J GGA proteins regulate retrograde transport of BACE1 from endosomes to the trans-Golgi network Mol Cell Neurosci 2005 29 453 461 10.1016/j.mcn.2005.03.014 15886016 · DOI
  72. Luo Y Bolon B Kahn S Bennett BD Babu-Khan S Denis P Fan W Kha H Zhang J Gong Y Mice deficient in BACE1, the Alzheimer's beta-secretase, have normal phenotype and abolished beta-amyloid generation Nat Neurosci 2001 4 231 232 10.1038/85059 11224535 · DOI · Paper page
  73. Ohno M Sametsky EA Younkin LH Oakley H Younkin SG Citron M Vassar R Disterhoft JF BACE1 deficiency rescues memory deficits and cholinergic dysfunction in a mouse model of Alzheimer's disease Neuron 2004 41 27 33 10.1016/S0896-6273(03)00810-9 14715132 · DOI · Paper page
  74. Ohno M Cole SL Yasvoina M Zhao J Citron M Berry R Disterhoft JF Vassar R BACE1 gene deletion prevents neuron loss and memory deficits in 5XFAD APP/PS1 transgenic mice Neurobiol Dis 2007 26 134 145 10.1016/j.nbd.2006.12.008 17258906 PMC1876698 · DOI · Paper page
  75. Yang LB Lindholm K Yan R Citron M Xia W Yang XL Beach T Sue L Wong P Price D Elevated beta-secretase expression and enzymatic activity detected in sporadic Alzheimer disease Nat Med 2003 9 3 4 10.1038/nm0103-3 12514700 · DOI · Paper page
  76. Johnston JA Liu WW Todd SA Coulson DT Murphy S Irvine GB Passmore AP Expression and activity of beta-site amyloid precursor protein cleaving enzyme in Alzheimer's disease Biochem Soc Trans 2005 33 1096 1100 10.1042/BST20051096 16246054 · DOI
  77. Dominguez D Tournoy J Hartmann D Huth T Cryns K Deforce S Serneels L Camacho IE Marjaux E Craessaerts K Phenotypic and biochemical analyses of BACE1- and BACE2-deficient mice J Biol Chem 2005 280 30797 30806 10.1074/jbc.M505249200 15987683 · DOI
  78. Hu X Hicks CW He W Wong P Macklin WB Trapp BD Yan R Bace1 modulates myelination in the central and peripheral nervous system Nat Neurosci 2006 9 1520 1525 10.1038/nn1797 17099708 · DOI · Paper page
  79. Vassar R Kovacs DM Yan R Wong PC The beta-secretase enzyme BACE in health and Alzheimer's disease: regulation, cell biology, function, and therapeutic potential J Neurosci 2009 29 12787 12794 10.1523/JNEUROSCI.3657-09.2009 19828790 PMC2879048 · DOI · Paper page
  80. Solans A Estivill X de La Luna S A new aspartyl protease on 21q22.3, BACE2, is highly similar to Alzheimer's amyloid precursor protein beta-secretase Cytogenet Cell Genet 2000 89 177 184 10.1159/000015608 10965118 · DOI
  81. Hussain I Powell DJ Howlett DR Chapman GA Gilmour L Murdock PR Tew DG Meek TD Chapman C Schneider K ASP1 (BACE2) cleaves the amyloid precursor protein at the beta-secretase site Mol Cell Neurosci 2000 16 609 619 10.1006/mcne.2000.0884 11083922 · DOI
  82. Bennett BD Babu-Khan S Loeloff R Louis JC Curran E Citron M Vassar R Expression analysis of BACE2 in brain and peripheral tissues J Biol Chem 2000 275 20647 20651 10.1074/jbc.M002688200 10749877 · DOI · Paper page
  83. Yan R Munzner JB Shuck ME Bienkowski MJ BACE2 functions as an alternative alpha-secretase in cells J Biol Chem 2001 276 34019 34027 10.1074/jbc.M105583200 11423558 · DOI
  84. Hook V Toneff T Bogyo M Greenbaum D Medzihradszky KF Neveu J Lane W Hook G Reisine T Inhibition of cathepsin B reduces beta-amyloid production in regulated secretory vesicles of neuronal chromaffin cells: evidence for cathepsin B as a candidate beta-secretase of Alzheimer's disease Biol Chem 2005 386 931 940 10.1515/BC.2005.108 16164418 · DOI
  85. Hook VY Kindy M Reinheckel T Peters C Hook G Genetic cathepsin B deficiency reduces beta-amyloid in transgenic mice expressing human wild-type amyloid precursor protein Biochem Biophys Res Commun 2009 386 284 288 10.1016/j.bbrc.2009.05.131 19501042 PMC2753505 · DOI
  86. Nikolaev A McLaughlin T O'Leary DD Tessier-Lavigne M APP binds DR6 to trigger axon pruning and neuron death via distinct caspases Nature 2009 457 981 989 10.1038/nature07767 19225519 PMC2677572 · DOI · Paper page
  87. Li H Wang B Wang Z Guo Q Tabuchi K Hammer RE Sudhof TC Zheng H Soluble amyloid precursor protein (APP) regulates transthyretin and Klotho gene expression without rescuing the essential function of APP Proc Natl Acad Sci USA 2010 107 17362 17367 10.1073/pnas.1012568107 20855613 PMC2951422 · DOI
  88. Yankner BA Dawes LR Fisher S Villa-Komaroff L Oster-Granite ML Neve RL Neurotoxicity of a fragment of the amyloid precursor associated with Alzheimer's disease Science 1989 245 417 420 10.1126/science.2474201 2474201 · DOI · Paper page
  89. Oster-Granite ML McPhie DL Greenan J Neve RL Age-dependent neuronal and synaptic degeneration in mice transgenic for the C terminus of the amyloid precursor protein J Neurosci 1996 16 6732 6741 8824314 PMC6579256
  90. Zhao G Mao G Tan J Dong Y Cui MZ Kim SH Xu X Identification of a new presenilin-dependent zeta-cleavage site within the transmembrane domain of amyloid precursor protein J Biol Chem 2004 279 50647 50650 10.1074/jbc.C400473200 15485850 · DOI
  91. Zhao G Tan J Mao G Cui MZ Xu X The same gamma-secretase accounts for the multiple intramembrane cleavages of APP J Neurochem 2007 100 1234 1246 10.1111/j.1471-4159.2006.04302.x 17241131 · DOI
  92. Sastre M Steiner H Fuchs K Capell A Multhaup G Condron MM Teplow DB Haass C Presenilin-dependent gamma-secretase processing of beta-amyloid precursor protein at a site corresponding to the S3 cleavage of Notch EMBO Rep 2001 2 835 841 10.1093/embo-reports/kve180 11520861 PMC1084035 · DOI
  93. Weidemann A Eggert S Reinhard FB Vogel M Paliga K Baier G Masters CL Beyreuther K Evin G A novel epsilon-cleavage within the transmembrane domain of the Alzheimer amyloid precursor protein demonstrates homology with Notch processing Biochemistry 2002 41 2825 2835 10.1021/bi015794o 11851430 · DOI
  94. Kimberly WT LaVoie MJ Ostaszewski BL Ye W Wolfe MS Selkoe DJ Gamma-secretase is a membrane protein complex comprised of presenilin, nicastrin, Aph-1, and Pen-2 Proc Natl Acad Sci USA 2003 100 6382 6387 10.1073/pnas.1037392100 12740439 PMC164455 · DOI
  95. Takasugi N Tomita T Hayashi I Tsuruoka M Niimura M Takahashi Y Thinakaran G Iwatsubo T The role of presenilin cofactors in the gamma-secretase complex Nature 2003 422 438 441 10.1038/nature01506 12660785 · DOI
  96. Kim J Schekman R The ins and outs of presenilin 1 membrane topology Proc Natl Acad Sci USA 2004 101 905 906 10.1073/pnas.0307297101 14732690 PMC327113 · DOI
  97. Borchelt DR Thinakaran G Eckman CB Lee MK Davenport F Ratovitsky T Prada CM Kim G Seekins S Yager D Familial Alzheimer's disease-linked presenilin 1 variants elevate Abeta1-42/1-40 ratio in vitro and in vivo Neuron 1996 17 1005 1013 10.1016/S0896-6273(00)80230-5 8938131 · DOI · Paper page
  98. Li YM Lai MT Xu M Huang Q DiMuzio-Mower J Sardana MK Shi XP Yin KC Shafer JA Gardell SJ Presenilin 1 is linked with gamma-secretase activity in the detergent solubilized state Proc Natl Acad Sci USA 2000 97 6138 6143 10.1073/pnas.110126897 10801983 PMC18571 · DOI
  99. Ahn K Shelton CC Tian Y Zhang X Gilchrist ML Sisodia SS Li YM Activation and intrinsic {gamma}-secretase activity of presenilin 1 Proc Natl Acad Sci USA 2010 PMC3003001 21115843
  100. Luo WJ Wang H Li H Kim BS Shah S Lee HJ Thinakaran G Kim TW Yu G Xu H PEN-2 and APH-1 coordinately regulate proteolytic processing of presenilin 1 J Biol Chem 2003 278 7850 7854 10.1074/jbc.C200648200 12522139 · DOI
  101. Francis R McGrath G Zhang J Ruddy DA Sym M Apfeld J Nicoll M Maxwell M Hai B Ellis MC aph-1 and pen-2 are required for Notch pathway signaling, gamma-secretase cleavage of betaAPP, and presenilin protein accumulation Dev Cell 2002 3 85 97 10.1016/S1534-5807(02)00189-2 12110170 · DOI
  102. Goutte C Tsunozaki M Hale VA Priess JR APH-1 is a multipass membrane protein essential for the Notch signaling pathway in Caenorhabditis elegans embryos Proc Natl Acad Sci USA 2002 99 775 779 10.1073/pnas.022523499 11792846 PMC117381 · DOI
  103. Edbauer D Winkler E Regula JT Pesold B Steiner H Haass C Reconstitution of gamma-secretase activity Nat Cell Biol 2003 5 486 488 10.1038/ncb960 12679784 · DOI
  104. Greenfield JP Xu H Greengard P Gandy S Seeger M Generation of the amyloid-beta peptide N terminus in Saccharomyces cerevisiae expressing human Alzheimer's amyloid-beta precursor protein J Biol Chem 1999 274 33843 33846 10.1074/jbc.274.48.33843 10567340 · DOI
  105. Zhou S Zhou H Walian PJ Jap BK CD147 is a regulatory subunit of the gamma-secretase complex in Alzheimer's disease amyloid beta-peptide production Proc Natl Acad Sci USA 2005 102 7499 7504 10.1073/pnas.0502768102 15890777 PMC1103709 · DOI
  106. Chen F Hasegawa H Schmitt-Ulms G Kawarai T Bohm C Katayama T Gu Y Sanjo N Glista M Rogaeva E TMP21 is a presenilin complex component that modulates gamma-secretase but not epsilon-secretase activity Nature 2006 440 1208 1212 10.1038/nature04667 16641999 · DOI
  107. Pardossi-Piquard R Bohm C Chen F Kanemoto S Checler F Schmitt-Ulms G St George-Hyslop P Fraser PE TMP21 transmembrane domain regulates gamma-secretase cleavage J Biol Chem 2009 284 28634 28641 10.1074/jbc.M109.059345 19710022 PMC2781407 · DOI
  108. Vetrivel KS Gong P Bowen JW Cheng H Chen Y Carter M Nguyen PD Placanica L Wieland FT Li YM Dual roles of the transmembrane protein p23/TMP21 in the modulation of amyloid precursor protein metabolism Mol Neurodegener 2007 2 4 10.1186/1750-1326-2-4 17288597 PMC1803014 · DOI
  109. He G Luo W Li P Remmers C Netzer WJ Hendrick J Bettayeb K Flajolet M Gorelick F Wennogle LP Gamma-secretase activating protein is a therapeutic target for Alzheimer's disease Nature 2010 467 95 98 10.1038/nature09325 20811458 PMC2936959 · DOI
  110. Cupers P Bentahir M Craessaerts K Orlans I Vanderstichele H Saftig P De Strooper B Annaert W The discrepancy between presenilin subcellular localization and gamma-secretase processing of amyloid precursor protein J Cell Biol 2001 154 731 740 10.1083/jcb.200104045 11502763 PMC2196466 · DOI
  111. Kovacs DM Fausett HJ Page KJ Kim TW Moir RD Merriam DE Hollister RD Hallmark OG Mancini R Felsenstein KM Alzheimer-associated presenilins 1 and 2: neuronal expression in brain and localization to intracellular membranes in mammalian cells Nat Med 1996 2 224 229 10.1038/nm0296-224 8574969 · DOI
  112. Haass C De Strooper B The presenilins in Alzheimer's disease--proteolysis holds the key Science 1999 286 916 919 10.1126/science.286.5441.916 10542139 · DOI · Paper page
  113. Wang R Tang P Wang P Boissy RE Zheng H Regulation of tyrosinase trafficking and processing by presenilins: partial loss of function by familial Alzheimer's disease mutation Proc Natl Acad Sci USA 2006 103 353 358 10.1073/pnas.0509822102 16384915 PMC1326180 · DOI
  114. Vetrivel KS Zhang YW Xu H Thinakaran G Pathological and physiological functions of presenilins Mol Neurodegener 2006 1 4 10.1186/1750-1326-1-4 16930451 PMC1513131 · DOI
  115. Tarassishin L Yin YI Bassit B Li YM Processing of Notch and amyloid precursor protein by gamma-secretase is spatially distinct Proc Natl Acad Sci USA 2004 101 17050 17055 10.1073/pnas.0408007101 15563588 PMC535399 · DOI
  116. Kopan R Schroeter EH Weintraub H Nye JS Signal transduction by activated mNotch: importance of proteolytic processing and its regulation by the extracellular domain Proc Natl Acad Sci USA 1996 93 1683 1688 10.1073/pnas.93.4.1683 8643690 PMC40002 · DOI
  117. Schroeter EH Kisslinger JA Kopan R Notch-1 signalling requires ligand-induced proteolytic release of intracellular domain Nature 1998 393 382 386 10.1038/30756 9620803 · DOI
  118. Sardi SP Murtie J Koirala S Patten BA Corfas G Presenilin-dependent ErbB4 nuclear signaling regulates the timing of astrogenesis in the developing brain Cell 2006 127 185 197 10.1016/j.cell.2006.07.037 17018285 · DOI
  119. Baek SH Ohgi KA Rose DW Koo EH Glass CK Rosenfeld MG Exchange of N-CoR corepressor and Tip60 coactivator complexes links gene expression by NF-kappaB and beta-amyloid precursor protein Cell 2002 110 55 67 10.1016/S0092-8674(02)00809-7 12150997 · DOI
  120. Kim HS Kim EM Lee JP Park CH Kim S Seo JH Chang KA Yu E Jeong SJ Chong YH C-terminal fragments of amyloid precursor protein exert neurotoxicity by inducing glycogen synthase kinase-3beta expression Faseb J 2003 17 1951 1953 12923068
  121. Pardossi-Piquard R Petit A Kawarai T Sunyach C Alves da Costa C Vincent B Ring S D'Adamio L Shen J Muller U Presenilin-dependent transcriptional control of the Abeta-degrading enzyme neprilysin by intracellular domains of betaAPP and APLP Neuron 2005 46 541 554 10.1016/j.neuron.2005.04.008 15944124 · DOI
  122. von Rotz RC Kohli BM Bosset J Meier M Suzuki T Nitsch RM Konietzko U The APP intracellular domain forms nuclear multiprotein complexes and regulates the transcription of its own precursor J Cell Sci 2004 117 4435 4448 10.1242/jcs.01323 15331662 · DOI
  123. Zhang YW Wang R Liu Q Zhang H Liao FF Xu H Presenilin/gamma-secretase-dependent processing of beta-amyloid precursor protein regulates EGF receptor expression Proc Natl Acad Sci USA 2007 104 10613 10618 10.1073/pnas.0703903104 17556541 PMC1888796 · DOI
  124. Liu Q Zerbinatti CV Zhang J Hoe HS Wang B Cole SL Herz J Muglia L Bu G Amyloid precursor protein regulates brain apolipoprotein E and cholesterol metabolism through lipoprotein receptor LRP1 Neuron 2007 56 66 78 10.1016/j.neuron.2007.08.008 17920016 PMC2045076 · DOI · Paper page
  125. Giliberto L Zhou D Weldon R Tamagno E De Luca P Tabaton M D'Adamio L Evidence that the Amyloid beta Precursor Protein-intracellular domain lowers the stress threshold of neurons and has a "regulated" transcriptional role Mol Neurodegener 2008 3 12 10.1186/1750-1326-3-12 18764939 PMC2538519 · DOI
  126. Kinoshita A Whelan CM Berezovska O Hyman BT The gamma secretase-generated carboxyl-terminal domain of the amyloid precursor protein induces apoptosis via Tip60 in H4 cells J Biol Chem 2002 277 28530 28536 10.1074/jbc.M203372200 12032152 · DOI
  127. Tamayev R Zhou D D'Adamio L The interactome of the amyloid beta precursor protein family members is shaped by phosphorylation of their intracellular domains Mol Neurodegener 2009 4 28 10.1186/1750-1326-4-28 19602287 PMC2723102 · DOI
  128. Park SA Shaked GM Bredesen DE Koo EH Mechanism of cytotoxicity mediated by the C31 fragment of the amyloid precursor protein Biochem Biophys Res Commun 2009 388 450 455 10.1016/j.bbrc.2009.08.042 19679105 PMC2838490 · DOI
  129. Gervais FG Xu D Robertson GS Vaillancourt JP Zhu Y Huang J LeBlanc A Smith D Rigby M Shearman MS Involvement of caspases in proteolytic cleavage of Alzheimer's amyloid-beta precursor protein and amyloidogenic A beta peptide formation Cell 1999 97 395 406 10.1016/S0092-8674(00)80748-5 10319819 · DOI
  130. Bredesen DE Neurodegeneration in Alzheimer's disease: caspases and synaptic element interdependence Mol Neurodegener 2009 4 27 10.1186/1750-1326-4-27 19558683 PMC2709109 · DOI
  131. Soriano S Lu DC Chandra S Pietrzik CU Koo EH The amyloidogenic pathway of amyloid precursor protein (APP) is independent of its cleavage by caspases J Biol Chem 2001 276 29045 29050 10.1074/jbc.M102456200 11397796 · DOI
  132. Lu DC Soriano S Bredesen DE Koo EH Caspase cleavage of the amyloid precursor protein modulates amyloid beta-protein toxicity J Neurochem 2003 87 733 741 10.1046/j.1471-4159.2003.02059.x 14535955 · DOI
  133. Galvan V Gorostiza OF Banwait S Ataie M Logvinova AV Sitaraman S Carlson E Sagi SA Chevallier N Jin K Reversal of Alzheimer's-like pathology and behavior in human APP transgenic mice by mutation of Asp664 Proc Natl Acad Sci USA 2006 103 7130 7135 10.1073/pnas.0509695103 16641106 PMC1459029 · DOI · Paper page
  134. Shankar GM Walsh DM Alzheimer's disease: synaptic dysfunction and Abeta Mol Neurodegener 2009 4 48 10.1186/1750-1326-4-48 19930651 PMC2788538 · DOI
  135. Jarrett JT Berger EP Lansbury PT Jr The carboxy terminus of the beta amyloid protein is critical for the seeding of amyloid formation: implications for the pathogenesis of Alzheimer's disease Biochemistry 1993 32 4693 4697 10.1021/bi00069a001 8490014 · DOI · Paper page
  136. Mori C Spooner ET Wisniewsk KE Wisniewski TM Yamaguch H Saido TC Tolan DR Selkoe DJ Lemere CA Intraneuronal Abeta42 accumulation in Down syndrome brain Amyloid 2002 9 88 102 12440481
  137. Espana J Gimenez-Llort L Valero J Minano A Rabano A Rodriguez-Alvarez J LaFerla FM Saura CA Intraneuronal beta-amyloid accumulation in the amygdala enhances fear and anxiety in Alzheimer's disease transgenic mice Biol Psychiatry 2010 67 513 521 10.1016/j.biopsych.2009.06.015 19664757 · DOI
  138. Yu C Nwabuisi-Heath E Laxton K Ladu MJ Endocytic pathways mediating oligomeric Abeta42 neurotoxicity Mol Neurodegener 2010 5 19 10.1186/1750-1326-5-19 20478062 PMC2881055 · DOI
  139. Morley JE Farr SA Banks WA Johnson SN Yamada KA Xu L A physiological role for amyloid-beta protein:enhancement of learning and memory J Alzheimers Dis 2010 19 441 449 19749407
  140. Plant LD Boyle JP Smith IF Peers C Pearson HA The production of amyloid beta peptide is a critical requirement for the viability of central neurons J Neurosci 2003 23 5531 5535 12843253 PMC6741264
  141. Plant LD Webster NJ Boyle JP Ramsden M Freir DB Peers C Pearson HA Amyloid beta peptide as a physiological modulator of neuronal 'A'-type K+ current Neurobiol Aging 2006 27 1673 1683 10.1016/j.neurobiolaging.2005.09.038 16271805 · DOI
  142. Minniti AN Rebolledo DL Grez PM Fadic R Aldunate R Volitakis I Cherny RA Opazo C Masters C Bush AI Intracellular amyloid formation in muscle cells of Abeta-transgenic Caenorhabditis elegans: determinants and physiological role in copper detoxification Mol Neurodegener 2009 4 2 10.1186/1750-1326-4-2 19126228 PMC2632641 · DOI
  143. King GD Scott Turner R Adaptor protein interactions: modulators of amyloid precursor protein metabolism and Alzheimer's disease risk? Exp Neurol 2004 185 208 219 10.1016/j.expneurol.2003.10.011 14736502 · DOI
  144. Rogelj B Mitchell JC Miller CC McLoughlin DM The X11/Mint family of adaptor proteins Brain Res Rev 2006 52 305 315 10.1016/j.brainresrev.2006.04.005 16764936 · DOI
  145. Borg JP 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 6241 8887653 PMC231626
  146. Borg JP Yang Y De Taddeo-Borg M Margolis B Turner RS The X11alpha protein slows cellular amyloid precursor protein processing and reduces Abeta40 and Abeta42 secretion J Biol Chem 1998 273 14761 14766 10.1074/jbc.273.24.14761 9614075 · DOI · Paper page
  147. Salcini AE Chen H Iannolo G De Camilli P Di Fiore PP Epidermal growth factor pathway substrate 15, Eps15 Int J Biochem Cell Biol 1999 31 805 809 10.1016/S1357-2725(99)00042-4 10481267 · DOI
  148. Sorkin A Cargo recognition during clathrin-mediated endocytosis: a team effort Curr Opin Cell Biol 2004 16 392 399 10.1016/j.ceb.2004.06.001 15261671 · DOI
  149. Maldonado-Baez L Wendland B Endocytic adaptors: recruiters, coordinators and regulators Trends Cell Biol 2006 16 505 513 10.1016/j.tcb.2006.08.001 16935508 · DOI
  150. Chyung JH Selkoe DJ Inhibition of receptor-mediated endocytosis demonstrates generation of amyloid beta-protein at the cell surface J Biol Chem 2003 278 51035 51043 10.1074/jbc.M304989200 14525989 · DOI · Paper page
  151. Carey RM Balcz BA Lopez-Coviella I Slack BE Inhibition of dynamin-dependent endocytosis increases shedding of the amyloid precursor protein ectodomain and reduces generation of amyloid beta protein BMC Cell Biol 2005 6 30 10.1186/1471-2121-6-30 16095541 PMC1208872 · DOI
  152. Cai D Leem JY Greenfield JP Wang P Kim BS Wang R Lopes KO Kim SH Zheng H Greengard P Presenilin-1 regulates intracellular trafficking and cell surface delivery of beta-amyloid precursor protein J Biol Chem 2003 278 3446 3454 10.1074/jbc.M209065200 12435726 · DOI
  153. Dumanchin C Czech C Campion D Cuif MH Poyot T Martin C Charbonnier F Goud B Pradier L Frebourg T Presenilins interact with Rab11, a small GTPase involved in the regulation of vesicular transport Hum Mol Genet 1999 8 1263 1269 10.1093/hmg/8.7.1263 10369872 · DOI · Paper page
  154. Scheper W Zwart R Sluijs P Annaert W Gool WA Baas F Alzheimer's presenilin 1 is a putative membrane receptor for rab GDP dissociation inhibitor Hum Mol Genet 2000 9 303 310 10.1093/hmg/9.2.303 10607841 · DOI
  155. Scheper W Zwart R Baas F Rab6 membrane association is dependent of Presenilin 1 and cellular phosphorylation events Brain Res Mol Brain Res 2004 122 17 23 10.1016/j.molbrainres.2003.11.013 14992812 · DOI
  156. Cai D Netzer WJ Zhong M Lin Y Du G Frohman M Foster DA Sisodia SS Xu H Gorelick FS Presenilin-1 uses phospholipase D1 as a negative regulator of beta-amyloid formation Proc Natl Acad Sci USA 2006 103 1941 1946 10.1073/pnas.0510708103 16449386 PMC1413665 · DOI
  157. Cai D Zhong M Wang R Netzer WJ Shields D Zheng H Sisodia SS Foster DA Gorelick FS Xu H Phospholipase D1 corrects impaired betaAPP trafficking and neurite outgrowth in familial Alzheimer's disease-linked presenilin-1 mutant neurons Proc Natl Acad Sci USA 2006 103 1936 1940 10.1073/pnas.0510710103 16449385 PMC1413666 · DOI
  158. Scherzer CR Offe K Gearing M Rees HD Fang G Heilman CJ Schaller C Bujo H Levey AI Lah JJ Loss of apolipoprotein E receptor LR11 in Alzheimer disease Arch Neurol 2004 61 1200 1205 10.1001/archneur.61.8.1200 15313836 · DOI · Paper page
  159. Grear KE Ling IF Simpson JF Furman JL Simmons CR Peterson SL Schmitt FA Markesbery WR Liu Q Crook JE Expression of SORL1 and a novel SORL1 splice variant in normal and Alzheimers disease brain Mol Neurodegener 2009 4 46 10.1186/1750-1326-4-46 19889229 PMC2776013 · DOI · Paper page
  160. Yamazaki H Bujo H Kusunoki J Seimiya K Kanaki T Morisaki N Schneider WJ Saito Y Elements of neural adhesion molecules and a yeast vacuolar protein sorting receptor are present in a novel mammalian low density lipoprotein receptor family member J Biol Chem 1996 271 24761 24768 10.1074/jbc.271.11.6483 8798746 · DOI
  161. Jacobsen L Madsen P Moestrup SK Lund AH Tommerup N Nykjaer A Sottrup-Jensen L Gliemann J Petersen CM Molecular characterization of a novel human hybrid-type receptor that binds the alpha2-macroglobulin receptor-associated protein J Biol Chem 1996 271 31379 31383 10.1074/jbc.271.49.31379 8940146 · DOI · Paper page
  162. Andersen OM Reiche J Schmidt V Gotthardt M Spoelgen R Behlke J von Arnim CA Breiderhoff T Jansen P Wu X Neuronal sorting protein-related receptor sorLA/LR11 regulates processing of the amyloid precursor protein Proc Natl Acad Sci USA 2005 102 13461 13466 10.1073/pnas.0503689102 16174740 PMC1224625 · DOI · Paper page
  163. Rogaeva E Meng Y Lee JH Gu Y Kawarai T Zou F Katayama T Baldwin CT Cheng R Hasegawa H The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease Nat Genet 2007 39 168 177 10.1038/ng1943 17220890 PMC2657343 · DOI · Paper page
  164. Trommsdorff M Borg JP Margolis B Herz J Interaction of cytosolic adaptor proteins with neuronal apolipoprotein E receptors and the amyloid precursor protein J Biol Chem 1998 273 33556 33560 10.1074/jbc.273.50.33556 9837937 · DOI
  165. Narita M Holtzman DM Schwartz AL Bu G Alpha2-macroglobulin complexes with and mediates the endocytosis of beta-amyloid peptide via cell surface low-density lipoprotein receptor-related protein J Neurochem 1997 69 1904 1911 10.1046/j.1471-4159.1997.69051904.x 9349534 · DOI
  166. Deane R Wu Z Sagare A Davis J Du Yan S Hamm K Xu F Parisi M LaRue B Hu HW LRP/amyloid beta-peptide interaction mediates differential brain efflux of Abeta isoforms Neuron 2004 43 333 344 10.1016/j.neuron.2004.07.017 15294142 · DOI · Paper page
  167. Ulery PG Beers J Mikhailenko I Tanzi RE Rebeck GW Hyman BT Strickland DK Modulation of beta-amyloid precursor protein processing by the low density lipoprotein receptor-related protein (LRP). Evidence that LRP contributes to the pathogenesis of Alzheimer's disease J Biol Chem 2000 275 7410 7415 10.1074/jbc.275.10.7410 10702315 · DOI · Paper page
  168. Cam JA Zerbinatti CV Knisely JM Hecimovic S Li Y Bu G The low density lipoprotein receptor-related protein 1B retains beta-amyloid precursor protein at the cell surface and reduces amyloid-beta peptide production J Biol Chem 2004 279 29639 29646 10.1074/jbc.M313893200 15126508 · DOI
  169. Tang MX Jacobs D Stern Y Marder K Schofield P Gurland B Andrews H Mayeux R Effect of oestrogen during menopause on risk and age at onset of Alzheimer's disease Lancet 1996 348 429 432 10.1016/S0140-6736(96)03356-9 8709781 · DOI
  170. Waring SC Rocca WA Petersen RC O'Brien PC Tangalos EG Kokmen E Postmenopausal estrogen replacement therapy and risk of AD: a population-based study Neurology 1999 52 965 970 10102413
  171. Baldereschi M Di Carlo A Lepore V Bracco L Maggi S Grigoletto F Scarlato G Amaducci L Estrogen-replacement therapy and Alzheimer's disease in the Italian Longitudinal Study on Aging Neurology 1998 50 996 1002 9566385
  172. Paganini-Hill A Estrogen replacement therapy--something to smile about Compend Contin Educ Dent Suppl 1998 S4 8 12089760
  173. Wise PM Dubal DB Wilson ME Rau SW Bottner M Rosewell KL Estradiol is a protective factor in the adult and aging brain: understanding of mechanisms derived from in vivo and in vitro studies Brain Res Brain Res Rev 2001 37 313 319 10.1016/S0165-0173(01)00136-9 11744096 · DOI
  174. Colton CA Brown CM Vitek MP Sex steroids, APOE genotype and the innate immune system Neurobiol Aging 2005 26 363 372 10.1016/j.neurobiolaging.2004.08.001 15639315 · DOI · Paper page
  175. Ghosh S Thakur MK PS1 expression is downregulated by gonadal steroids in adult mouse brain Neurochem Res 2008 33 365 369 10.1007/s11064-007-9424-8 17703361 · DOI
  176. Greenfield JP Leung LW Cai D Kaasik K Gross RS Rodriguez-Boulan E Greengard P Xu H Estrogen lowers Alzheimer beta-amyloid generation by stimulating trans-Golgi network vesicle biogenesis J Biol Chem 2002 277 12128 12136 10.1074/jbc.M110009200 11823458 · DOI
  177. Xu H Gouras GK Greenfield JP Vincent B Naslund J Mazzarelli L Fried G Jovanovic JN Seeger M Relkin NR Estrogen reduces neuronal generation of Alzheimer beta-amyloid peptides Nat Med 1998 4 447 451 10.1038/nm0498-447 9546791 · DOI
  178. Xu H Wang R Zhang YW Zhang X Estrogen, beta-amyloid metabolism/trafficking, and Alzheimer's disease Ann N Y Acad Sci 2006 1089 324 342 10.1196/annals.1386.036 17261779 · DOI
  179. Zhang S Huang Y Zhu YC Yao T Estrogen stimulates release of secreted amyloid precursor protein from primary rat cortical neurons via protein kinase C pathway Acta Pharmacol Sin 2005 26 171 176 10.1111/j.1745-7254.2005.00538.x 15663894 · DOI
  180. Buxbaum JD Gandy SE Cicchetti P Ehrlich ME Czernik AJ Fracasso RP Ramabhadran TV Unterbeck AJ Greengard P Processing of Alzheimer beta/A4 amyloid precursor protein: modulation by agents that regulate protein phosphorylation Proc Natl Acad Sci USA 1990 87 6003 6006 10.1073/pnas.87.15.6003 2116015 PMC54458 · DOI
  181. Caporaso GL Gandy SE Buxbaum JD Ramabhadran TV Greengard P Protein phosphorylation regulates secretion of Alzheimer beta/A4 amyloid precursor protein Proc Natl Acad Sci USA 1992 89 3055 3059 10.1073/pnas.89.7.3055 1557413 PMC48802 · DOI
  182. Gillespie SL Golde TE Younkin SG Secretory processing of the Alzheimer amyloid beta/A4 protein precursor is increased by protein phosphorylation Biochem Biophys Res Commun 1992 187 1285 1290 10.1016/0006-291X(92)90442-N 1417805 · DOI
  183. Hung AY Haass C Nitsch RM Qiu WQ Citron M Wurtman RJ Growdon JH Selkoe DJ Activation of protein kinase C inhibits cellular production of the amyloid beta-protein J Biol Chem 1993 268 22959 22962 8226807
  184. Gandy S Czernik AJ Greengard P Phosphorylation of Alzheimer disease amyloid precursor peptide by protein kinase C and Ca2+/calmodulin-dependent protein kinase II Proc Natl Acad Sci USA 1988 85 6218 6221 10.1073/pnas.85.16.6218 3137567 PMC281937 · DOI
  185. Xu H Greengard P Gandy S Regulated formation of Golgi secretory vesicles containing Alzheimer beta-amyloid precursor protein J Biol Chem 1995 270 23243 23245 10.1074/jbc.270.40.23243 7559474 · DOI
  186. Xu H Sweeney D Greengard P Gandy S Metabolism of Alzheimer beta-amyloid precursor protein: regulation by protein kinase A in intact cells and in a cell-free system Proc Natl Acad Sci USA 1996 93 4081 4084 10.1073/pnas.93.9.4081 8633020 PMC39490 · DOI
  187. Driscoll I Resnick SM Testosterone and cognition in normal aging and Alzheimer's disease: an update Curr Alzheimer Res 2007 4 33 45 10.2174/156720507779939878 17316164 · DOI
  188. Goodenough S Engert S Behl C Testosterone stimulates rapid secretory amyloid precursor protein release from rat hypothalamic cells via the activation of the mitogen-activated protein kinase pathway Neurosci Lett 2000 296 49 52 10.1016/S0304-3940(00)01622-0 11099831 · DOI
  189. Gouras GK Xu H Gross RS Greenfield JP Hai B Wang R Greengard P Testosterone reduces neuronal secretion of Alzheimer's beta-amyloid peptides Proc Natl Acad Sci USA 2000 97 1202 1205 10.1073/pnas.97.3.1202 10655508 PMC15568 · DOI
  190. McAllister C Long J Bowers A Walker A Cao P Honda S Harada N Staufenbiel M Shen Y Li R Genetic targeting aromatase in male amyloid precursor protein transgenic mice down-regulates beta-secretase (BACE1) and prevents Alzheimer-like pathology and cognitive impairment J Neurosci 2010 30 7326 7334 10.1523/JNEUROSCI.1180-10.2010 20505099 PMC3506430 · DOI

Cited by

Sorted by citations

Authors
Zhang, Y.-W., Thompson, R., Zhang, H., & Xu, H.
Affiliations
  • Xiamen University (CN)
  • Sanford Burnham Prebys Medical Discovery Institute (US)
Corresponding author
  • Zhang, Yun-wu
  • Xu, Huaxi
ORCID
Venue
Molecular Brain
Publisher
Springer Science and Business Media LLC
Published
2011
Volume
4
Issue
1
Pages
3
ISSN
1756-6606 (ISSN-L)
DOI
10.1186/1756-6606-4-3
PMC
PMC3022812
OpenAlex
W2110495164
Cited by
983
References
22
Citations by year
2026: 61 · 2025: 86 · 2024: 86 · 2023: 87 · 2022: 82 · 2021: 91 · 2020: 86 · 2019: 60 · 2018: 57 · 2017: 45 · 2016: 52 · 2015: 48 · 2014: 34 · 2013: 41 · 2012: 41
FWCI
4.90
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Molecular Brain (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Alzheimer's Association
  • American Health Assistance Foundation
  • National Natural Science Foundation of China (2009ZX09103, 30973150)
  • Fok Ying Tung Education Foundation
  • National Institutes of Health
  • Program for New Century Excellent Talents in University
  • Fundamental Research Funds for the Central Universities
  • National Institute on Aging (R01AG038710, R01AG030197, R03AG034366, R01AG021173)
  • National Institute of Neurological Disorders and Stroke (R01NS046673)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
Alzheimer's disease, amyloid precursor protein, APP processing, amyloid-beta, amyloid plaques, beta-secretase, gamma-secretase, alpha-secretase, caspase cleavage, soluble APP alpha
MeSH terms
Alzheimer Disease, Animals, Humans, Isoenzymes, Signal Transduction, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Caspases, Amyloid Precursor Protein Secretases, Plaque, Amyloid

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review