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Cited by 201Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsDementia and Cognitive Impairment Research

The β-Secretase-Derived C-Terminal Fragment of βAPP, C99, But Not Aβ, Is a Key Contributor to Early Intraneuronal Lesions in Triple-Transgenic Mouse Hippocampus

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Lauritzen, Inger, Pardossi-Piquard, Raphaëlle, Bauer, Charlotte, Brigham, Elizabeth, Abraham, Jean-Daniel, Ranaldi, Sébastien, Fraser, Paul, St-George-Hyslop, Peter +5 more·2012·The Journal of Neuroscience
DOI 10.1523/jneurosci.2775-12.2012PMC PMC5019353
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Abstract

Triple-transgenic mice (3xTgAD) overexpressing Swedish-mutated β-amyloid precursor protein (βAPP swe), P310L-Tau (Tau P301L), and physiological levels of M146V-presenilin-1 (PS1 M146V) display extracellular amyloid-β peptides (Aβ) deposits and Tau tangles. More disputed is the observation that these mice accumulate intraneuronal Aβ that has been linked to synaptic dysfunction and cognitive deficits. Here, we provide immunohistological, genetic, and pharmacological evidences for early, age-dependent, and hippocampus-specific accumulation of the β-secretase-derived βAPP fragment C99 that is observed from 3 months of age and enhanced by pharmacological blockade of γ-secretase. Notably, intracellular Aβ is only detectable several months later and appears, as is the case of C99, in enlarged cathepsin B-positive structures, while extracellular Aβ deposits are detected ∼12 months of age and beyond. Early C99 production occurs mainly in the CA1/subicular interchange area of the hippocampus corresponding to the first region exhibiting plaques and tangles in old mice. Furthermore, the comparison of 3xTgAD mice with double-transgenic mice bearing the βAPP swe and Tau P301L mutations but expressing endogenous PS1 (2xTgAD) demonstrate that C99 accumulation is not accounted for by a loss of function triggered by PS1 mutation that would have prevented C99 secondary cleavage by γ-secretase. Together, our work identifies C99 as the earliest βAPP catabolite and main contributor to the intracellular βAPP-related immunoreactivity in 3xTgAD mice, suggesting its implication as an initiator of the neurodegenerative process and cognitive alterations taking place in this mouse model.

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  • APP-βCTF has been previously linked to lysosomal dysfunction in AD models involving overexpressed forms of FAD-mutated APP with or without additional overexpression of other mutated human AD genes, and in iPSC generated Ts21 neurons.

    “APP-␤CTF has also been previously linked to lysosomal dysfunction in AD models involving overexpressed forms of FAD-mutated APP with or without additional overexpression of other mutated human AD genes (Lauritzen et al., 2012(Lauritzen et al., , 2016;;Yang et al., 2014;Kaur et al., 2017;Bourgeois et al., 2018), and in iPSC generated Ts21 neurons (Hung and Livesey, 2018).”

    From Lysosomal Dysfunction in Down Syndrome Is APP-Dependent and Mediated by APP-βCTF (C99) (2019) · cites this paper as Lauritzen et al., 2012

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References 68 · Cited by 201

Research works printed but not linked: 79

  1. Alves da Costa C Sunyach C Pardossi-Piquard R Sevalle J Vincent B Boyer N Kawarai T Girardot N St George-Hyslop P Checler F Presenilin-dependent gamma-secretase-mediated control of p53-associated cell death in Alzheimer's disease J Neurosci 2006 26 6377 6385 16763046 PMC6675197
  2. Andrau D Dumanchin-Njock C Ayral E Vizzavona J Farzan M Boisbrun M Fulcrand P Hernandez JF Martinez J Lefranc-Jullien S Checler F BACE1- and BACE2-expressing human cells: characterization of beta-amyloid precursor protein-derived catabolites, design of a novel fluorimetric assay, and identification of new in vitro inhibitors J Biol Chem 2003 278 25859 25866 12736275
  3. Asai M Yagishita S Iwata N Saido TC Ishiura S Maruyama K An alternative metabolic pathway of amyloid precursor protein C-terminal fragments via cathepsin B in a human neuroglioma model FASEB J 2011 25 3720 3730 21746863
  4. Barelli H Lebeau A Vizzavona J Delaere P Chevallier N Drouot C Marambaud P Ancolio K Buxbaum JD Khorkova O Heroux J Characterization of new polyclonal antibodies specific for 40 and 42 amino acid-long amyloid beta peptides: their use to examine the cell biology of presenilins and the immunohistochemistry of sporadic Alzheimer's disease and cerebral amyloid angiopathy cases Mol Med 1997 3 695 707 9392006 PMC2230230
  5. Bayer TA Wirths O Intracellular accumulation of amyloid-Beta - a predictor for synaptic dysfunction and neuron loss in Alzheimer's disease Front Aging Neurosci 2010 2 8 20552046 PMC2879032
  6. Belyaev ND Nalivaeva NN Makova NZ Turner AJ Neprilysin gene expression requires binding of the amyloid precursor protein intracellular domain to its promoter: implications for Alzheimer disease EMBO Rep 2009 10 94 100 19057576 PMC2613207
  7. Belyaev ND Kellett KA Beckett C Makova NZ Revett TJ Nalivaeva NN Hooper NM Turner AJ 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 41454 20961856 PMC3009870
  8. Brigham E Pharmacokinetic and pharmacodynamic investigation of ELND006, a novel APP-selective gamma-secretase inhibitor, on amyloid concentrations in the brain, CSF and plasma of multiple nonclinical species following oral administration International Conference on Alzheimer's Disease 2010
  9. Brunden KR Zhang B Carroll J Yao Y Potuzak JS Hogan AM Iba M James MJ Xie SX Ballatore C Smith AB 3rd Epothilone D improves microtubule density, axonal integrity, and cognition in a transgenic mouse model of tauopathy J Neurosci 2010 30 13861 13866 20943926 PMC2958430
  10. Butler D Hwang J Estick C Nishiyama A Kumar SS Baveghems C Young-Oxendine HB Wisniewski ML Charalambides A Bahr BA Protective effects of positive lysosomal modulation in Alzheimer's disease transgenic mouse models PLoS One 2011 6 e20501 21695208 PMC3112200
  11. Caccamo A Majumder S Richardson A Strong R Oddo S Molecular interplay between mammalian target of rapamycin (mTOR), amyloid-beta, and Tau: effects on cognitive impairments J Biol Chem 2010 285 13107 13120 20178983 PMC2857107
  12. Cai D Leem JY Greenfield JP Wang P Kim BS Wang R Lopes KO Kim SH Zheng H Greengard P Sisodia SS Presenilin-1 regulates intracellular trafficking and cell surface delivery of beta-amyloid precursor protein J Biol Chem 2003 278 3446 3454 12435726
  13. Cai Z Zhao B Li K Zhang L Li C Quazi SH Tan Y Mammalian target of rapamycin: a valid therapeutic target through the autophagy pathway for Alzheimer's disease? J Neurosci Res 2012 90 1105 1118 22344941
  14. Cataldo AM Nixon RA Enzymatically active lysosomal proteases are associated with amyloid deposits in Alzheimer brain Proc Natl Acad Sci U S A 1990 87 3861 3865 1692625 PMC54003
  15. Cataldo AM Peterhoff CM Troncoso JC Gomez-Isla T Hyman BT Nixon RA Endocytic pathway abnormalities precede amyloid beta deposition in sporadic Alzheimer's disease and Down syndrome: differential effects of APOE genotype and presenilin mutations Am J Pathol 2000 157 277 286 10880397 PMC1850219
  16. Checler F Processing of the beta-amyloid precursor protein and its regulation in Alzheimer's disease J Neurochem 1995 65 1431 1444 7561836
  17. Chen F Gu Y Hasegawa H Ruan X Arawaka S Fraser P Westaway D Mount H St George-Hyslop P Presenilin 1 mutations activate gamma 42-secretase but reciprocally inhibit epsilon-secretase cleavage of amyloid precursor protein (APP) and S3-cleavage of notch J Biol Chem 2002 277 36521 36526 12119298
  18. Chen F Hasegawa H Schmitt-Ulms G Kawarai T Bohm C Katayama T Gu Y Sanjo N Glista M Rogaeva E Wakutani Y TMP21 is a presenilin complex component that modulates gamma-secretase but not epsilon-secretase activity Nature 2006 440 1208 1212 16641999
  19. Chen F Carboxyl-terminal fragments of Alzheimer beta-amyloid precursor protein accumulate in restricted and unpredicted intracellular compartments in presenilin 1-deficient cells J Biol Chem 2000 275 36794 36802 10962005
  20. Chishti MA Early-onset amyloid deposition and cognitive deficits in transgenic mice expressing a double mutant form of amyloid precursor protein 695 J Biol Chem 2001 276 21562 21570 11279122
  21. Choi SH Park CH Koo JW Seo JH Kim HS Jeong SJ Lee JH Kim SS Suh YH Memory impairment and cholinergic dysfunction by centrally administered Abeta and carboxyl-terminal fragment of Alzheimer's APP in mice FASEB J 2001 15 1816 1818 11481240
  22. Comery TA Martone RL Aschmies S Atchison KP Diamantidis G Gong X Zhou H Kreft AF Pangalos MN Sonnenberg-Reines J Jacobsen JS Acute gamma-secretase inhibition improves contextual fear conditioning in the Tg2576 mouse model of Alzheimer's disease J Neurosci 2005 25 8898 8902 16192379 PMC6725598
  23. Flammang B Pardossi-Piquard R Sevalle J Debayle D Dabert-Gay AS Thevenet A Lauritzen I Checler F Evidence that the Amyloid-beta Protein Precursor Intracellular Domain, AICD, Derives From beta-Secretase-Generated C-Terminal Fragment J Alzheimers Dis 2012 30 145 153 22406447
  24. Funderburk SF Marcellino BK Yue Z Cell “self-eating” (autophagy) mechanism in Alzheimer's disease Mt Sinai J Med 2010 77 59 68 20101724 PMC2835623
  25. Ghosal K Vogt DL Liang M Shen Y Lamb BT Pimplikar SW Alzheimer's disease-like pathological features in transgenic mice expressing the APP intracellular domain Proc Natl Acad Sci U S A 2009 106 18367 18372 19837693 PMC2762847
  26. Glenner GG Wong CW Alzheimer's disease and Down's syndrome: sharing of a unique cerebrovascular amyloid fibril protein Biochem Biophys Res Commun 1984 122 1131 1135 6236805
  27. Golde TE Estus S Younkin LH Selkoe DJ Younkin SG Processing of the amyloid protein precursor to potentially amyloidogenic derivatives Science 1992 255 728 730 1738847
  28. Goodger ZV Rajendran L Trutzel A Kohli BM Nitsch RM Konietzko U Nuclear signaling by the APP intracellular domain occurs predominantly through the amyloidogenic processing pathway J Cell Sci 2009 122 3703 3714 19773363
  29. Grundke-Iqbal I Iqbal K Tung YC Quinlan M Wisniewski HM Binder LI Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology Proc Natl Acad Sci U S A 1986 83 4913 4917 3088567 PMC323854
  30. Haass C Koo EH Mellon A Hung AY Selkoe DJ Targeting of cell-surface beta-amyloid precursor protein to lysosomes: alternative processing into amyloid-bearing fragments Nature 1992 357 500 503 1608449
  31. Hardy JA Higgins GA Alzheimer's disease: the amyloid cascade hypothesis Science 1992 256 184 185 1566067
  32. He G Luo W Li P Remmers C Netzer WJ Hendrick J Bettayeb K Flajolet M Gorelick F Wennogle LP Greengard P Gamma-secretase activating protein is a therapeutic target for Alzheimer's disease Nature 2010 467 95 98 20811458 PMC2936959
  33. Hirata-Fukae C Li HF Hoe HS Gray AJ Minami SS Hamada K Niikura T Hua F Tsukagoshi-Nagai H Horikoshi-Sakuraba Y Mughal M Females exhibit more extensive amyloid, but not tau, pathology in an Alzheimer transgenic model Brain Res 2008 1216 92 103 18486110
  34. Horikoshi Y Sakaguchi G Becker AG Gray AJ Duff K Aisen PS Yamaguchi H Maeda M Kinoshita N Matsuoka Y Development of Abeta terminal end-specific antibodies and sensitive ELISA for Abeta variant Biochem Biophys Res Commun 2004 319 733 737 15184044
  35. Hsiao K Chapman P Nilsen S Eckman C Harigaya Y Younkin S Yang F Cole G Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice Science 1996 274 99 102 8810256
  36. Jager S Leuchtenberger S Martin A Czirr E Wesselowski J Dieckmann M Waldron E Korth C Koo EH Heneka M Weggen S alpha-secretase mediated conversion of the amyloid precursor protein derived membrane stub C99 to C83 limits Abeta generation J Neurochem 2009 111 1369 1382 19804379
  37. Jarrett JT Berger EP Lansbury PT Jr The C-terminus of the beta protein is critical in amyloidogenesis Ann N Y Acad Sci 1993 695 144 148 8239273
  38. Konietzko U AICD Nuclear Signaling and its Possible Contribution to Alzheimer's Disease Curr Alzheimer Res 2011 21605035
  39. Lazarov O Morfini GA Pigino G Gadadhar A Chen X Robinson J Ho H Brady ST Sisodia SS Impairments in fast axonal transport and motor neuron deficits in transgenic mice expressing familial Alzheimer's disease-linked mutant presenilin 1 J Neurosci 2007 27 7011 7020 17596450 PMC2801050
  40. Lefranc-Jullien S Sunyach C Checler F APPepsilon, the epsilon-secretase-derived N-terminal product of the beta-amyloid precursor protein, behaves as a type I protein and undergoes alpha-, beta-, and gamma-secretase cleavages J Neurochem 2006 97 807 817 16524370
  41. Majumder S Richardson A Strong R Oddo S Inducing autophagy by rapamycin before, but not after, the formation of plaques and tangles ameliorates cognitive deficits PLoS One 2011 6 e25416 21980451 PMC3182203
  42. Martone RL Begacestat (GSI-953): a novel, selective thiophene sulfonamide inhibitor of amyloid precursor protein gamma-secretase for the treatment of Alzheimer's disease J Pharmacol Exp Ther 2009 331 598 608 19671883
  43. Masters CL Simms G Weinman NA Multhaup G McDonald BL Beyreuther K Amyloid plaque core protein in Alzheimer disease and Down syndrome Proc Natl Acad Sci U S A 1985 82 4245 4249 3159021 PMC397973
  44. Mastrangelo MA Bowers WJ Detailed immunohistochemical characterization of temporal and spatial progression of Alzheimer's disease-related pathologies in male triple-transgenic mice BMC Neurosci 2008 9 81 18700006 PMC2527610
  45. Mitani Y Yarimizu J Saita K Uchino H Akashiba H Shitaka Y Ni K Matsuoka N Differential Effects between gamma-Secretase Inhibitors and Modulators on Cognitive Function in Amyloid Precursor Protein-Transgenic and Nontransgenic Mice J Neurosci 2012 32 2037 2050 22323718 PMC6621706
  46. Mueller-Steiner S Zhou Y Arai H Roberson ED Sun B Chen J Wang X Yu G Esposito L Mucke L Gan L Antiamyloidogenic and neuroprotective functions of cathepsin B: implications for Alzheimer's disease Neuron 2006 51 703 714 16982417
  47. Nalbantoglu J Tirado-Santiago G Lahsaini A Poirier J Goncalves O Verge G Momoli F Welner SA Massicotte G Julien JP Shapiro ML Impaired learning and LTP in mice expressing the carboxy terminus of the Alzheimer amyloid precursor protein Nature 1997 387 500 505 9168112
  48. Netzer WJ Powell C Nong Y Blundell J Wong L Duff K Flajolet M Greengard P Lowering beta-amyloid levels rescues learning and memory in a Down syndrome mouse model PLoS One 2010 5 e10943 20532168 PMC2880593
  49. Netzer WJ Dou F Cai D Veach D Jean S Li Y Bornmann WG Clarkson B Xu H Greengard P Gleevec inhibits beta-amyloid production but not Notch cleavage Proc Natl Acad Sci U S A 2003 100 12444 12449 14523244 PMC218777
  50. Nixon RA Autophagy in neurodegenerative disease: friend, foe or turncoat? Trends Neurosci 2006 29 528 535 16859759
  51. Nixon RA Yang DS Autophagy failure in Alzheimer's disease--locating the primary defect Neurobiol Dis 2011 43 38 45 21296668 PMC3096679
  52. Nixon RA Cataldo AM Mathews PM The endosomal-lysosomal system of neurons in Alzheimer's disease pathogenesis: a review Neurochem Res 2000 25 1161 1172 11059790
  53. Oddo S Caccamo A Tseng B Cheng D Vasilevko V Cribbs DH LaFerla FM Blocking Abeta42 accumulation delays the onset and progression of tau pathology via the C terminus of heat shock protein70-interacting protein: a mechanistic link between Abeta and tau pathology J Neurosci 2008 28 12163 12175 19020010 PMC6671718
  54. 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
  55. Ozaki T Li Y Kikuchi H Tomita T Iwatsubo T Nakagawara A The intracellular domain of the amyloid precursor protein (AICD) enhances the p53-mediated apoptosis Biochem Biophys Res Commun 2006 351 57 63 17054906
  56. Pardossi-Piquard R Checler F The physiology of the beta-amyloid precursor protein intracellular domain AICD J Neurochem 2012 120 Suppl 1 109 124 22122663
  57. Pardossi-Piquard R Dunys J Yu G St George-Hyslop P Alves da Costa C Checler F Neprilysin activity and expression are controlled by nicastrin J Neurochem 2006 97 1052 1056 16606360
  58. 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 19710022 PMC2781407
  59. Pardossi-Piquard R Petit A Kawarai T Sunyach C Alves da Costa C Vincent B Ring S D'Adamio L Shen J Muller U St George Hyslop P Presenilin-dependent transcriptional control of the Abeta-degrading enzyme neprilysin by intracellular domains of betaAPP and APLP Neuron 2005 46 541 554 15944124
  60. Pasternak SH Callahan JW Mahuran DJ The role of the endosomal/lysosomal system in amyloid-beta production and the pathophysiology of Alzheimer's disease: reexamining the spatial paradox from a lysosomal perspective J Alzheimers Dis 2004 6 53 65 15004328
  61. Petit A Bihel F Alves da Costa C Pourquie O Checler F Kraus JL New protease inhibitors prevent gamma-secretase-mediated production of Abeta40/42 without affecting Notch cleavage Nat Cell Biol 2001 3 507 511 11331880
  62. Phiel CJ Wilson CA Lee VM Klein PS GSK-3alpha regulates production of Alzheimer's disease amyloid-beta peptides Nature 2003 423 435 439 12761548
  63. Pigino G Morfini G Pelsman A Mattson MP Brady ST Busciglio J Alzheimer's presenilin 1 mutations impair kinesin-based axonal transport J Neurosci 2003 23 4499 4508 12805290 PMC6740780
  64. Portelius E Brinkmalm G Tran AJ Zetterberg H Westman-Brinkmalm A Blennow K Identification of novel APP/Abeta isoforms in human cerebrospinal fluid Neurodegener Dis 2009 6 87 94 19229112
  65. Ryan KA Pimplikar SW Activation of GSK-3 and phosphorylation of CRMP2 in transgenic mice expressing APP intracellular domain J Cell Biol 2005 171 327 335 16230462 PMC2171208
  66. Schroeter S Brigham E Motter R Nishioka C Guido T Khan K Kholodenko D Tanaka P Soriano F Quinn K Goldbach E APP-selective gamma secretase inhibitor ELND006 effects on brain parenchymal and vascular amyloid beta International Conference on Alzheimer's Disease 2010
  67. Sevalle J Ayral E Hernandez JF Martinez J Checler F Pharmacological evidences for DFK167-sensitive presenilin-independent gamma-secretase-like activity J Neurochem 2009 110 275 283 19457123
  68. Suh YH An etiological role of amyloidogenic carboxyl-terminal fragments of the beta-amyloid precursor protein in Alzheimer's disease J Neurochem 1997 68 1781 1791 9109502
  69. Tamayev R Matsuda S Arancio O D'Adamio L beta- but not gamma-secretase proteolysis of APP causes synaptic and memory deficits in a mouse model of dementia EMBO Mol Med 2012 PMC3376850 22170863
  70. 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 19828790 PMC2879048
  71. Vingtdeux V Hamdane M Begard S Loyens A Delacourte A Beauvillain JC Buee L Marambaud P Sergeant N Intracellular pH regulates amyloid precursor protein intracellular domain accumulation Neurobiol Dis 2007a 25 686 696 17207630
  72. Vingtdeux V Hamdane M Loyens A Gele P Drobeck H Begard S Galas MC Delacourte A Beauvillain JC Buee L Sergeant N Alkalizing drugs induce accumulation of amyloid precursor protein by-products in luminal vesicles of multivesicular bodies J Biol Chem 2007b 282 18197 18205 17468104
  73. 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 15331662
  74. Walsh DM Teplow DB Alzheimer's Disease and the Amyloid beta-Protein Prog Mol Biol Transl Sci 2012 107 101 124 22482449
  75. Weggen S Eriksen JL Sagi SA Pietrzik CU Golde TE Koo EH Abeta42-lowering nonsteroidal anti-inflammatory drugs preserve intramembrane cleavage of the amyloid precursor protein (APP) and ErbB-4 receptor and signaling through the APP intracellular domain J Biol Chem 2003 278 30748 30754 12777371
  76. Winton MJ Lee EB Sun E Wong MM Leight S Zhang B Trojanowski JQ Lee VM Intraneuronal APP, not free Abeta peptides in 3xTg-AD mice: implications for tau versus Abeta-mediated Alzheimer neurodegeneration J Neurosci 2011 31 7691 7699 21613482 PMC3118598
  77. Wirths O Dins A Bayer TA AbetaPP accumulation and/or intraneuronal amyloid-beta accumulation? The 3xTg-AD mouse model revisited J Alzheimers Dis 2012 28 897 904 22112547
  78. Yang DS Stavrides P Mohan PS Kaushik S Kumar A Ohno M Schmidt SD Wesson D Bandyopadhyay U Jiang Y Pawlik M Reversal of autophagy dysfunction in the TgCRND8 mouse model of Alzheimer's disease ameliorates amyloid pathologies and memory deficits Brain 2010 134 258 277 21186265 PMC3009842
  79. Zhang B Higuchi M Yoshiyama Y Ishihara T Forman MS Martinez D Joyce S Trojanowski JQ Lee VM Retarded axonal transport of R406W mutant tau in transgenic mice with a neurodegenerative tauopathy J Neurosci 2004 24 4657 4667 15140937 PMC6729383

Authors
Lauritzen, I., Pardossi-Piquard, R., Bauer, C., Brigham, E., Abraham, J.-D., Ranaldi, S., Fraser, P., St-George-Hyslop, P., Le Thuc, O., Espin, V., Chami, L., Dunys, J., & Checler, F.
Affiliations
  • Centre National de la Recherche Scientifique (FR)
  • Elan Pharmaceuticals, Inc. (Ireland) (IE)
  • University of Toronto (CA)
Corresponding author
Checler, Frédéric
ORCID
Venue
The Journal of Neuroscience
Publisher
Society for Neuroscience
Published
2012-11-14
Volume
32
Issue
46
Pages
16243-16255
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
DOI
10.1523/jneurosci.2775-12.2012
PMC
PMC5019353
OpenAlex
W2061123524
Cited by
201
References
68
Citations by year
2026: 7 · 2025: 9 · 2024: 17 · 2023: 10 · 2022: 19 · 2021: 19 · 2020: 23 · 2019: 20 · 2018: 16 · 2017: 16 · 2016: 19 · 2015: 10 · 2014: 8 · 2013: 8
FWCI
5.57
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Neuroscience (publishedVersion, other-oa)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, other-oa)
Funders
  • Wellcome Trust (089703, 081864)
  • Medical Research Council (MC_G1000734)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
beta-secretase, C99, amyloid precursor protein, intraneuronal amyloid-beta, triple transgenic mouse model, 3xTg-AD mice, presenilin 1, gamma-secretase inhibition, cathepsin B, hippocampus, P301L tau, Alzheimer's disease, neurodegeneration, synaptic dysfunction
MeSH terms
Aging, Animals, Electrophoresis, Polyacrylamide Gel, Enzyme-Linked Immunosorbent Assay, Hippocampus, Immunohistochemistry, Interneurons, Mice, Transgenic, Peptide Fragments, Blotting, Western, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, tau Proteins, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Immunoprecipitation, Mice, Presenilin-1, Amyloid Precursor Protein Secretases

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