CoChat
Sign Up
Cited by 263Alzheimer's disease research and treatmentsAutophagy in Disease and TherapyMitochondrial Function and Pathology

Accumulation of amyloid precursor protein C-terminal fragments triggers mitochondrial structure, function, and mitophagy defects in Alzheimer’s disease models and human brains

Open access
Vaillant-Beuchot, Loan, Mary, Arnaud, Pardossi-Piquard, Raphaëlle, Bourgeois, Alexandre, Lauritzen, Inger, Eysert, Fanny, Kinoshita, Paula Fernanda, Cazareth, Julie +13 more·2021·Acta Neuropathologica
DOI 10.1007/s00401-020-02234-7PMC PMC7785558
Open this paper in CoChat — free accountOpen PDF

Abstract

Several lines of recent evidence indicate that the amyloid precursor protein-derived C-terminal fragments (APP-CTFs) could correspond to an etiological trigger of Alzheimer’s disease (AD) pathology. Altered mitochondrial homeostasis is considered an early event in AD development. However, the specific contribution of APP-CTFs to mitochondrial structure, function, and mitophagy defects remains to be established. Here, we demonstrate in neuroblastoma SH-SY5Y cells expressing either APP Swedish mutations, or the β-secretase-derived APP-CTF fragment (C99) combined with β- and γ-secretase inhibition, that APP-CTFs accumulation independently of Aβ triggers excessive mitochondrial morphology alteration (i.e., size alteration and cristae disorganization) associated with enhanced mitochondrial reactive oxygen species production. APP-CTFs accumulation also elicit basal mitophagy failure illustrated by enhanced conversion of LC3, accumulation of LC3-I and/or LC3-II, non-degradation of SQSTM1/p62, inconsistent Parkin and PINK1 recruitment to mitochondria, enhanced levels of membrane and matrix mitochondrial proteins, and deficient fusion of mitochondria with lysosomes. We confirm the contribution of APP-CTFs accumulation to morphological mitochondria alteration and impaired basal mitophagy in vivo in young 3xTgAD transgenic mice treated with γ-secretase inhibitor as well as in adeno-associated-virus-C99 injected mice. Comparison of aged 2xTgAD and 3xTgAD mice indicates that, besides APP-CTFs, an additional contribution of Aβ to late-stage mitophagy activation occurs. Importantly, we report on mitochondrial accumulation of APP-CTFs in human post-mortem sporadic AD brains correlating with mitophagy failure molecular signature. Since defective mitochondria homeostasis plays a pivotal role in AD pathogenesis, targeting mitochondrial dysfunctions and/or mitophagy by counteracting early APP-CTFs accumulation may represent relevant therapeutic interventions in AD.

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 · 10.1007/s00401-020-02234-7

Cites

9 of 9 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?

  • Previous studies demonstrated the accumulation of amyloid-beta precursor protein (APP) and its products amyloid β (Aβ40 and Aβ42) and C-terminal fragments (APP-CTF) in the outer mitochondrial membrane through association with TOMM complex (including Tom20/40 proteins), which inhibits mitophagy.

    “Previous studies demonstrated the accumulation of amyloid-beta precursor protein (APP) and its product amyloid β (Aβ40 and Aβ42) and C-terminal fragments (APP-CTF) in the outer mitochondrial membrane through association with TOMM complex (including Tom20/40 proteins), which inhibits mitophagy (21,22).”

    From Alzheimer's Disease–Associated Amyloid-β Precursor Protein Prevents Aging Stress–Induced Mitophagy and Fumarate Depletion to Improve Antitumor Immunity (2025) · cites this paper as [22]

    Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

    Experimental — accuracy not yet measured

  • Dysfunctional autophagy leads to accumulation of APP C-terminal fragments and Aβ, as well as hyperphosphorylated tau, directly linking autophagy failure to the two central pathological hallmarks of AD.

    “Furthermore, dysfunctional autophagy leads to accumulation of APP C-terminal fragments and Aβ, as well as hyperphosphorylated tau, directly linking autophagy failure to the two central pathological hallmarks of AD [137].”

    From Toward a Unified Framework in Molecular Neurobiology of Alzheimer’s Disease: Revisiting the Pathophysiological Hypotheses (2026) · cites this paper as [137]

    The Discussion (page not provided) describes an amplifying loop in which lysosomal–autophagic dysfunction triggers lysosomal APP-CTF accumulation. The Results section on human AD brains reports correlations between mitophagy markers and Aβ or phosphorylated tau, but does not show that autophagy failure causes either to accumulate. The claimed causal link to both pathological hallmarks therefore goes beyond this paper's evidence. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Increased accumulation of APP and its processed peptides in mitochondria of AD neurons and effects on mitochondrial dynamics and mitophagy have been documented.

    “Increased accumulation of APP and its processed peptides in the mitochondria of AD neurons and their effects on mitochondrial dynamics and mitophagy have been documented (21–24).”

    From Alzheimer's Disease–Associated Amyloid-β Precursor Protein Prevents Aging Stress–Induced Mitophagy and Fumarate Depletion to Improve Antitumor Immunity (2025) · cites this paper as [22]

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: 79

  1. [1]Allen GF Toth R James J Ganley IG Loss of iron triggers PINK1/Parkin-independent mitophagy EMBO Rep 2013 14 1127 1135 10.1038/embor.2013.168 24176932 PMC3981094 · DOI
  2. [3]Anandatheerthavarada HK Devi L Mitochondrial translocation of amyloid precursor protein and its cleaved products: relevance to mitochondrial dysfunction in Alzheimer's disease Rev Neurosci 2007 18 343 354 10.1177/1073858407303536 19544621 · DOI · Paper page
  3. [5]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 10.1096/fj.11-182154 21746863 · DOI
  4. [6]Berger-Sweeney J McPhie DL Arters JA Greenan J Oster-Granite ML Neve RL Impairments in learning and memory accompanied by neurodegeneration in mice transgenic for the carboxyl-terminus of the amyloid precursor protein Brain Res Mol Brain Res 1999 66 150 162 10.1016/s0169-328x(99)00014-5 10095087 · DOI
  5. [8]Bobba A Amadoro G Valenti D Corsetti V Lassandro R Atlante A Mitochondrial respiratory chain Complexes I and IV are impaired by beta-amyloid via direct interaction and through Complex I-dependent ROS production, respectively Mitochondrion 2013 13 298 311 10.1016/j.mito.2013.03.008 23562762 · DOI
  6. [9]Bolte S Cordelieres FP A guided tour into subcellular colocalization analysis in light microscopy J Microsc 2006 224 213 232 10.1111/j.1365-2818.2006.01706.x 17210054 · DOI
  7. [10]Boon WC van den Buuse M Wegener N Martin S Chua HK Bush AI Behavioural phenotype of APPC100.V717F transgenic mice over-expressing a mutant Abeta-bearing fragment is associated with reduced NMDA receptor density Behav Brain Res 2010 209 27 35 10.1016/j.bbr.2010.01.013 20085783 · DOI
  8. [11]Bourgeois A Lauritzen I Lorivel T Bauer C Checler F Pardossi-Piquard R Intraneuronal accumulation of C99 contributes to synaptic alterations, apathy-like behavior, and spatial learning deficits in 3xTgAD and 2xTgAD mice Neurobiol Aging 2018 71 21 31 10.1016/j.neurobiolaging.2018.06.038 30071370 · DOI
  9. [12]Burns MP Zhang L Rebeck GW Querfurth HW Moussa CE Parkin promotes intracellular Abeta1-42 clearance Hum Mol Genet 2009 18 3206 3216 10.1093/hmg/ddp258 19483198 PMC2733820 · DOI
  10. [13]Bussiere R Lacampagne A Reiken S Liu X Scheuerman V Zalk R Amyloid beta production is regulated by beta2-adrenergic signaling-mediated post-translational modifications of the ryanodine receptor J Biol Chem 2017 292 10153 10168 10.1074/jbc.M116.743070 28476886 PMC5473221 · DOI
  11. [14]Checler F Processing of the beta-amyloid precursor protein and its regulation in Alzheimer's disease J Neurochem 1995 65 1431 1444 10.1046/j.1471-4159.1995.65041431.x 7561836 · DOI
  12. [15]Chen JX Yan SS Role of mitochondrial amyloid-beta in Alzheimer's disease J Alzheimers Dis 2010 20 Suppl 2 S569 578 10.3233/JAD-2010-100357 20463403 · DOI
  13. [18]da Costa CA Ancolio K Checler F Wild-type but not Parkinson's disease-related ala-53 → Thr mutant alpha-synuclein protects neuronal cells from apoptotic stimuli J Biol Chem 2000 275 24065 24069 10.1074/jbc.M002413200 10818098 · DOI
  14. [20]Del Prete D Suski JM Oules B Debayle D Gay AS Lacas-Gervais S Localization and processing of the amyloid-beta protein precursor in mitochondria-associated membranes J Alzheimers Dis 2017 55 1549 1570 10.3233/JAD-160953 27911326 PMC5181669 · DOI
  15. [21]Devi L Ohno M Mitochondrial dysfunction and accumulation of the beta-secretase-cleaved C-terminal fragment of APP in Alzheimer's disease transgenic mice Neurobiol Dis 2012 45 417 424 10.1016/j.nbd.2011.09.001 21933711 PMC3225635 · DOI
  16. [22]Duchen MR Surin A Jacobson J Imaging mitochondrial function in intact cells Methods Enzymol 2003 361 353 389 10.1016/S0076-6879(03)61019-0 12624920 · DOI
  17. [23]Dunys J Valverde A Checler F Are N- and C-terminally truncated Abeta species key pathological triggers in Alzheimer's disease? J Biol Chem 2018 293 15419 15428 10.1074/jbc.R118.003999 30143530 PMC6177599 · DOI
  18. [24]Emmerzaal TL Rodenburg RJ Tanila H Verweij V Kiliaan AJ Kozicz T Age-dependent decrease of mitochondrial complex II activity in a familial mouse model for Alzheimer's disease J Alzheimers Dis 2018 66 75 82 10.3233/JAD-180337 30248054 · DOI
  19. [25]Evin G Zhu A Holsinger RM Masters CL Li QX Proteolytic processing of the Alzheimer's disease amyloid precursor protein in brain and platelets J Neurosci Res 2003 74 386 392 10.1002/jnr.10745 14598315 · DOI
  20. [26]Falcon-Perez JM Nazarian R Sabatti C Dell'Angelica EC Distribution and dynamics of Lamp1-containing endocytic organelles in fibroblasts deficient in BLOC-3 J Cell Sci 2005 118 5243 5255 10.1242/jcs.02633 16249233 · DOI
  21. [27]Fedeli C Filadi R Rossi A Mammucari C Pizzo P PSEN2 (presenilin 2) mutants linked to familial Alzheimer disease impair autophagy by altering Ca(2+) homeostasis Autophagy 2019 15 2044 2062 10.1080/15548627.2019.1596489 30892128 PMC6844518 · DOI
  22. [29]Flammang B Pardossi-Piquard R Sevalle J Debayle D Dabert-Gay AS Thevenet A 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 10.3233/JAD-2012-112186 22406447 · DOI
  23. [30]Flannery PJ Trushina E Mitochondrial dynamics and transport in Alzheimer's disease Mol Cell Neurosci 2019 98 109 120 10.1016/j.mcn.2019.06.009 31216425 PMC6614006 · DOI
  24. [31]Goiran T Duplan E Chami M Bourgeois A El Manaa W Rouland L Beta-amyloid precursor protein intracellular domain controls mitochondrial function by modulating phosphatase and tensin homolog-induced kinase 1 transcription in cells and in Alzheimer mice models Biol Psychiatry 2017 10.1016/j.biopsych.2017.04.011 28587718 · DOI
  25. [32]Goiran T Duplan E Rouland L El Manaa W Lauritzen I Dunys J Nuclear p53-mediated repression of autophagy involves PINK1 transcriptional down-regulation Cell Death Differ 2018 25 873 884 10.1038/s41418-017-0016-0 29352272 PMC5943347 · DOI
  26. [33]Gonzalez AE Munoz VC Cavieres VA Bustamante HA Cornejo VH Januario YC Autophagosomes cooperate in the degradation of intracellular C-terminal fragments of thesoso amyloid precursor protein via the MVB/lysosomal pathway FASEB J 2017 31 2446 2459 10.1096/fj.201600713R 28254759 · DOI
  27. [34]Hauptmann S Scherping I Drose S Brandt U Schulz KL Jendrach M Mitochondrial dysfunction: an early event in Alzheimer pathology accumulates with age in AD transgenic mice Neurobiol Aging 2009 30 1574 1586 10.1016/j.neurobiolaging.2007.12.005 18295378 · DOI · Paper page
  28. [35]Hu Y Li XC Wang ZH Luo Y Zhang X Liu XP Tau accumulation impairs mitophagy via increasing mitochondrial membrane potential and reducing mitochondrial Parkin Oncotarget 2016 7 17356 17368 10.18632/oncotarget.7861 26943044 PMC4951217 · DOI
  29. [36]Hung COY Livesey FJ Altered gamma-secretase processing of APP disrupts lysosome and autophagosome function in monogenic Alzheimer's disease Cell Rep 2018 25 3647–3660 e3642 10.1016/j.celrep.2018.11.095 PMC6315085 30590039 · DOI · Paper page
  30. [37]Jazvinscak Jembrek M Slade N Hof PR Simic G The interactions of p53 with tau and Ass as potential therapeutic targets for Alzheimer's disease Prog Neurobiol 2018 168 104 127 10.1016/j.pneurobio.2018.05.001 29733887 · DOI
  31. [39]Kaur G Pawlik M Gandy SE Ehrlich ME Smiley JF Levy E Lysosomal dysfunction in the brain of a mouse model with intraneuronal accumulation of carboxyl terminal fragments of the amyloid precursor protein Mol Psychiatry 2017 22 981 989 10.1038/mp.2016.189 27777419 PMC5405008 · DOI
  32. [40]Kim SH Vlkolinsky R Cairns N Lubec G Decreased levels of complex III core protein 1 and complex V beta chain in brains from patients with Alzheimer's disease and Down syndrome Cell Mol Life Sci 2000 57 1810 1816 10.1007/pl00000661 11130185 PMC11146938 · DOI
  33. [41]Kwart D Gregg A Scheckel C Murphy EA Paquet D Duffield M A Large panel of isogenic APP and PSEN1 mutant human iPSC neurons reveals shared endosomal abnormalities mediated by APP beta-CTFs, not abeta Neuron 2019 104 1022 10.1016/j.neuron.2019.11.010 31805257 · DOI · Paper page
  34. [42]Lauritzen I Becot A Bourgeois A Pardossi-Piquard R Biferi MG Barkats M Targeting gamma-secretase triggers the selective enrichment of oligomeric APP-CTFs in brain extracellular vesicles from Alzheimer cell and mouse models Transl Neurodegener 2019 8 35 10.1186/s40035-019-0176-6 31827783 PMC6894230 · DOI
  35. [43]Lauritzen I Pardossi-Piquard R Bauer C Brigham E Abraham JD Ranaldi S The beta-secretase-derived C-terminal fragment of betaAPP, C99, but not abeta, is a key contributor to early intraneuronal lesions in triple-transgenic mouse hippocampus J Neurosci 2012 32 16243 16255 10.1523/JNEUROSCI.2775-12.2012 23152608 PMC5019353 · DOI · Paper page
  36. [44]Lauritzen I Pardossi-Piquard R Bourgeois A Becot A Checler F Does intraneuronal accumulation of carboxyl-terminal fragments of the amyloid precursor protein trigger early neurotoxicity in Alzheimer's disease? Curr Alzheimer Res 2019 16 453 457 10.2174/1567205016666190325092841 30907322 · DOI
  37. [45]Lauritzen I Pardossi-Piquard R Bourgeois A Pagnotta S Biferi MG Barkats M Intraneuronal aggregation of the beta-CTF fragment of APP (C99) induces Abeta-independent lysosomal-autophagic pathology Acta Neuropathol 2016 132 257 276 10.1007/s00401-016-1577-6 27138984 PMC4947121 · DOI · Paper page
  38. [46]Leuner K Muller WE Reichert AS From mitochondrial dysfunction to amyloid beta formation: novel insights into the pathogenesis of Alzheimer's disease Mol Neurobiol 2012 46 186 193 10.1007/s12035-012-8307-4 22833458 · DOI
  39. [47]Lonskaya I Shekoyan AR Hebron ML Desforges N Algarzae NK Moussa CE Diminished parkin solubility and co-localization with intraneuronal amyloid-beta are associated with autophagic defects in Alzheimer's disease J Alzheimers Dis 2013 33 231 247 10.3233/JAD-2012-121141 22954671 · DOI
  40. [48]Lustbader JW Cirilli M Lin C Xu HW Takuma K Wang N ABAD directly links Abeta to mitochondrial toxicity in Alzheimer's disease Science 2004 304 448 452 10.1126/science.1091230 15087549 · DOI · Paper page
  41. [49]Manczak M Calkins MJ Reddy PH Impaired mitochondrial dynamics and abnormal interaction of amyloid beta with mitochondrial protein Drp1 in neurons from patients with Alzheimer's disease: implications for neuronal damage Hum Mol Genet 2011 20 2495 2509 10.1093/hmg/ddr139 21459773 PMC3109997 · DOI
  42. [50]Manczak M Kandimalla R Yin X Reddy PH Hippocampal mutant APP and amyloid beta-induced cognitive decline, dendritic spine loss, defective autophagy, mitophagy and mitochondrial abnormalities in a mouse model of Alzheimer's disease Hum Mol Genet 2018 27 1332 1342 10.1093/hmg/ddy042 29408999 PMC6455948 · DOI
  43. [51]Martin-Maestro P Gargini R Perry G Avila J Garcia-Escudero V PARK2 enhancement is able to compensate mitophagy alterations found in sporadic Alzheimer's disease Hum Mol Genet 2016 25 792 806 10.1093/hmg/ddv616 26721933 PMC4743695 · DOI
  44. [52]Mitani Y Yarimizu J Saita K Uchino H Akashiba H Shitaka Y 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 10.1523/JNEUROSCI.4264-11.2012 22323718 PMC6621706 · DOI · Paper page
  45. [53]Mondragon-Rodriguez S Gu N Manseau F Williams S Alzheimer's transgenic model is characterized by very early brain network alterations and beta-CTF fragment accumulation: reversal by beta-secretase inhibition Front Cell Neurosci 2018 12 121 10.3389/fncel.2018.00121 29867356 PMC5952042 · DOI
  46. [54]Nalbantoglu J Tirado-Santiago G Lahsaini A Poirier J Goncalves O Verge G Impaired learning and LTP in mice expressing the carboxy terminus of the Alzheimer amyloid precursor protein Nature 1997 387 500 505 10.1038/387500a0 9168112 · DOI
  47. [55]Nhan HS Chiang K Koo EH The multifaceted nature of amyloid precursor protein and its proteolytic fragments: friends and foes Acta Neuropathol 2015 129 1 19 10.1007/s00401-014-1347-2 25287911 PMC4282969 · DOI
  48. [57]Osellame LD Blacker TS Duchen MR Cellular and molecular mechanisms of mitochondrial function Best Pract Res Clin Endocrinol Metab 2012 26 711 723 10.1016/j.beem.2012.05.003 23168274 PMC3513836 · DOI
  49. [58]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 10.1523/JNEUROSCI.16-21-06732.1996 8824314 PMC6579256 · DOI
  50. [59]Oules B Del Prete D Greco B Zhang X Lauritzen I Sevalle J Ryanodine receptor blockade reduces amyloid-beta load and memory impairments in Tg2576 mouse model of Alzheimer disease J Neurosci 2012 32 11820 11834 10.1523/JNEUROSCI.0875-12.2012 22915123 PMC3458216 · DOI
  51. [60]Pagani L Eckert A Amyloid-Beta interaction with mitochondria Int J Alzheimers Dis 2011 2011 925050 10.4061/2011/925050 21461357 PMC3065051 · DOI · Paper page
  52. [61]Pavlov PF Wiehager B Sakai J Frykman S Behbahani H Winblad B Mitochondrial gamma-secretase participates in the metabolism of mitochondria-associated amyloid precursor protein FASEB J 2011 25 78 88 10.1096/fj.10-157230 20833873 · DOI
  53. [62]Pera M Alcolea D Sanchez-Valle R Guardia-Laguarta C Colom-Cadena M Badiola N Distinct patterns of APP processing in the CNS in autosomal-dominant and sporadic Alzheimer disease Acta Neuropathol 2013 125 201 213 10.1007/s00401-012-1062-9 23224319 PMC3623032 · DOI
  54. [63]Pera M Larrea D Guardia-Laguarta C Montesinos J Velasco KR Agrawal RR Increased localization of APP-C99 in mitochondria-associated ER membranes causes mitochondrial dysfunction in Alzheimer disease EMBO J 2017 36 3356 3371 10.15252/embj.201796797 29018038 PMC5731665 · DOI
  55. [64]Pickles S Vigie P Youle RJ Mitophagy and quality control mechanisms in mitochondrial maintenance Curr Biol 2018 28 R170 R185 10.1016/j.cub.2018.01.004 29462587 PMC7255410 · DOI · Paper page
  56. [65]Piras A Collin L Gruninger F Graff C Ronnback A Autophagic and lysosomal defects in human tauopathies: analysis of post-mortem brain from patients with familial Alzheimer disease, corticobasal degeneration and progressive supranuclear palsy Acta Neuropathol Commun 2016 4 22 10.1186/s40478-016-0292-9 26936765 PMC4774096 · DOI · Paper page
  57. [66]Pulina MV Hopkins M Haroutunian V Greengard P Bustos V C99 selectively accumulates in vulnerable neurons in Alzheimer's disease Alzheimers Dement 2020 16 273 282 10.1016/j.jalz.2019.09.002 31677937 · DOI
  58. [67]Rah JC Kim HS Kim SS Bach JH Kim YS Park CH Effects of carboxyl-terminal fragment of Alzheimer's amyloid precursor protein and amyloid beta-peptide on the production of cytokines and nitric oxide in glial cells FASEB J 2001 15 1463 1465 10.1096/fj.00-0724fje 11387258 · DOI
  59. [68]Reddy PH Beal MF Amyloid beta, mitochondrial dysfunction and synaptic damage: implications for cognitive decline in aging and Alzheimer's disease Trends Mol Med 2008 14 45 53 10.1016/j.molmed.2007.12.002 18218341 PMC3107703 · DOI · Paper page
  60. [69]Reddy PH Yin X Manczak M Kumar S Pradeepkiran JA Vijayan M Mutant APP and amyloid beta-induced defective autophagy, mitophagy, mitochondrial structural and functional changes and synaptic damage in hippocampal neurons from Alzheimer's disease Hum Mol Genet 2018 27 2502 2516 10.1093/hmg/ddy154 29701781 PMC6031001 · DOI
  61. [70]Robinson KM Janes MS Pehar M Monette JS Ross MF Hagen TM Selective fluorescent imaging of superoxide in vivo using ethidium-based probes Proc Natl Acad Sci USA 2006 103 15038 15043 10.1073/pnas.0601945103 17015830 PMC1586181 · DOI · Paper page
  62. [71]Rojansky R Cha MY Chan DC Elimination of paternal mitochondria in mouse embryos occurs through autophagic degradation dependent on PARKIN and MUL1 Elife 2016 10.7554/eLife.17896 27852436 PMC5127638 · DOI
  63. [72]Rossi MJ Pekkurnaz G Powerhouse of the mind: mitochondrial plasticity at the synapse Curr Opin Neurobiol 2019 57 149 155 10.1016/j.conb.2019.02.001 30875521 PMC6629504 · DOI
  64. [73]Rustin P Chretien D Bourgeron T Gerard B Rotig A Saudubray JM Biochemical and molecular investigations in respiratory chain deficiencies Clin Chim Acta 1994 228 35 51 10.1016/0009-8981(94)90055-8 7955428 · DOI
  65. [74]Schreiner B Hedskog L Wiehager B Ankarcrona M Amyloid-beta peptides are generated in mitochondria-associated endoplasmic reticulum membranes J Alzheimers Dis 2015 43 369 374 10.3233/JAD-132543 25096627 · DOI
  66. [75]Sena LA Chandel NS Physiological roles of mitochondrial reactive oxygen species Mol Cell 2012 48 158 167 10.1016/j.molcel.2012.09.025 23102266 PMC3484374 · DOI · Paper page
  67. [76]Sorrentino V Romani M Mouchiroud L Beck JS Zhang H D'Amico D Enhancing mitochondrial proteostasis reduces amyloid-beta proteotoxicity Nature 2017 552 187 193 10.1038/nature25143 29211722 PMC5730497 · DOI · Paper page
  68. [77]Tamayev R D'Adamio L Inhibition of gamma-secretase worsens memory deficits in a genetically congruous mouse model of Danish dementia Mol Neurodegener 2012 7 19 10.1186/1750-1326-7-19 22537414 PMC3407505 · DOI · Paper page
  69. [78]van Dyck CH Anti-amyloid-beta monoclonal antibodies for Alzheimer's disease: pitfalls and promise Biol Psychiatry 2018 83 311 319 10.1016/j.biopsych.2017.08.010 28967385 PMC5767539 · DOI · Paper page
  70. [79]Wang X Su B Siedlak SL Moreira PI Fujioka H Wang Y Amyloid-beta overproduction causes abnormal mitochondrial dynamics via differential modulation of mitochondrial fission/fusion proteins Proc Natl Acad Sci USA 2008 105 19318 19323 10.1073/pnas.0804871105 19050078 PMC2614759 · DOI · Paper page
  71. [80]Wang X Wang W Li L Perry G Lee HG Zhu X Oxidative stress and mitochondrial dysfunction in Alzheimer's disease Biochim Biophys Acta 2014 1842 1240 1247 10.1016/j.bbadis.2013.10.015 24189435 PMC4007397 · DOI · Paper page
  72. [81]Wang Y Wu F Pan H Zheng W Feng C Wang Y Lost region in amyloid precursor protein (APP) through TALEN-mediated genome editing alters mitochondrial morphology Sci Rep 2016 6 22244 10.1038/srep22244 26924205 PMC4770288 · DOI
  73. [82]Wilkins HM Swerdlow RH Amyloid precursor protein processing and bioenergetics Brain Res Bull 2017 133 71 79 10.1016/j.brainresbull.2016.08.009 27545490 PMC5316384 · DOI
  74. [83]Xu LL Shen Y Wang X Wei LF Wang P Yang H Mitochondrial dynamics changes with age in an APPsw/PS1dE9 mouse model of Alzheimer's disease NeuroReport 2017 28 222 228 10.1097/WNR.0000000000000739 28118288 PMC5321113 · DOI
  75. [84]Yang C Cai CZ Song JX Tan JQ Durairajan SSK Iyaswamy A NRBF2 is involved in the autophagic degradation process of APP-CTFs in Alzheimer disease models Autophagy 2017 13 2028 2040 10.1080/15548627.2017.1379633 28980867 PMC5788544 · DOI · Paper page
  76. [85]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
  77. [86]Ye X Sun X Starovoytov V Cai Q Parkin-mediated mitophagy in mutant hAPP neurons and Alzheimer's disease patient brains Hum Mol Genet 2015 24 2938 2951 10.1093/hmg/ddv056 25678552 PMC4406302 · DOI · Paper page
  78. [87]Yoo SM Jung YK A molecular approach to mitophagy and mitochondrial dynamics Mol Cells 2018 41 18 26 10.14348/molcells.2018.2277 29370689 PMC5792708 · DOI
  79. [88]Zhang L Trushin S Christensen TA Bachmeier BV Gateno B Schroeder A Altered brain energetics induces mitochondrial fission arrest in Alzheimer's disease Sci Rep 2016 6 18725 10.1038/srep18725 26729583 PMC4700525 · DOI

Cited by

Sorted by citations

Authors
Vaillant-Beuchot, L., Mary, A., Pardossi-Piquard, R., Bourgeois, A., Lauritzen, I., Eysert, F., Kinoshita, P. F., Cazareth, J., Badot, C., Fragaki, K., Bussiere, R., Martin, C., Mary, R., Bauer, C., Pagnotta, S., Paquis-Flucklinger, V., Buée-Scherrer, V., Buée, L., Lacas-Gervais, S., Checler, F., & Chami, M.
Affiliations
  • Centre National de la Recherche Scientifique (FR)
  • Université Côte d'Azur (FR)
  • Inserm (FR)
Corresponding author
Chami, Mounia
ORCID
Venue
Acta Neuropathologica
Publisher
Springer Science and Business Media LLC
Published
2020-10-20
Volume
141
Issue
1
Pages
39-65
ISSN
  • 0001-6322 (ISSN-L)
  • 1432-0533
DOI
10.1007/s00401-020-02234-7
PMC
PMC7785558
OpenAlex
W3092964313
Cited by
263
References
9
Citations by year
2026: 37 · 2025: 47 · 2024: 52 · 2023: 54 · 2022: 45 · 2021: 25 · 2020: 3
FWCI
19.25
Type
journal article
Language
en
Open access
Licence
Locations
  • Acta Neuropathologica (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, other-oa)
  • Open Repository and Bibliography (University of Luxembourg) (submittedVersion, other-oa)
  • Spiral (Imperial College London) (submittedVersion, cc-by)
Funders
  • Fondation Vaincre Alzheimer (# FR18-035)
  • LABEX DISTALZ
  • FAPESP (#2018/14289-6)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Keywords
amyloid precursor protein, C-terminal fragment, Alzheimer's disease, mitophagy, mitochondrial dysfunction, mitochondrial morphology, reactive oxygen species, LC3, p62, Parkin, PINK1, APP Swedish mutation, amyloid-beta, 3xTg-AD mice, postmortem brain, mitochondrial homeostasis
MeSH terms
Aged, Aged, 80 and over, Alzheimer Disease, Animals, Autopsy, Brain, Cell Line, Female, Humans, Mitochondria, Peptide Fragments, Aspartic Acid Endopeptidases, Amyloid beta-Protein Precursor, Reactive Oxygen Species, Mice, Membrane Potential, Mitochondrial, Amyloid Precursor Protein Secretases, Mitophagy

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