CoChat
Sign Up
Cited by 69Alzheimer's disease research and treatmentsParkinson's Disease Mechanisms and TreatmentsDementia and Cognitive Impairment Research

APOE4 exacerbates α-synuclein seeding activity and contributes to neurotoxicity in Alzheimer’s disease with Lewy body pathology

Open access
Jin, Yunjung, Li, Fuyao, Sonoustoun, Berkiye, Kondru, Naveen Chandra, Martens, Yuka A., Qiao, Wenhui, Heckman, Michael G., Ikezu, Tadafumi C. +11 more·2022·Acta Neuropathologica
DOI 10.1007/s00401-022-02421-8PMC PMC9107450
Open this paper in CoChat — free accountOpen PDF

Abstract

Approximately half of Alzheimer’s disease (AD) brains have concomitant Lewy pathology at autopsy, suggesting that α-synuclein (α-SYN) aggregation is a regulated event in the pathogenesis of AD. Genome-wide association studies revealed that the ε4 allele of the apolipoprotein E (APOE4) gene, the strongest genetic risk factor for AD, is also the most replicated genetic risk factor for Lewy body dementia (LBD), signifying an important role of APOE4 in both amyloid-β (Aβ) and α-SYN pathogenesis. How APOE4 modulates α-SYN aggregation in AD is unclear. In this study, we aimed to determine how α-SYN is associated with AD-related pathology and how APOE4 impacts α-SYN seeding and toxicity. We measured α-SYN levels and their association with other established AD-related markers in brain samples from autopsy-confirmed AD patients (N = 469), where 54% had concomitant LB pathology (AD + LB). We found significant correlations between the levels of α-SYN and those of Aβ40, Aβ42, tau and APOE, particularly in insoluble fractions of AD + LB. Using a real-time quaking-induced conversion (RT-QuIC) assay, we measured the seeding activity of soluble α-SYN and found that α-SYN seeding was exacerbated by APOE4 in the AD cohort, as well as a small cohort of autopsy-confirmed LBD brains with minimal Alzheimer type pathology. We further fractionated the soluble AD brain lysates by size exclusion chromatography (SEC) ran on fast protein liquid chromatography (FPLC) and identified the α-SYN species (~ 96 kDa) that showed the strongest seeding activity. Finally, using human induced pluripotent stem cell (iPSC)-derived neurons, we showed that amplified α-SYN aggregates from AD + LB brain of patients with APOE4 were highly toxic to neurons, whereas the same amount of α-SYN monomer was not toxic. Our findings suggest that the presence of LB pathology correlates with AD-related pathologies and that APOE4 exacerbates α-SYN seeding activity and neurotoxicity, providing mechanistic insight into how APOE4 affects α-SYN pathogenesis 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/s00401-022-02421-8

Cites

5 of 5 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?

  • Biochemical studies indicate that APOE4 increases the seeding potential of α-synuclein.

    “Biochemical studies indicate that APOE4 increases the seeding potential of αSyn131,132, and further mouse studies have shown that APOE4 alters the proteolytic processing of αSyn.”

    From Multifaceted roles of APOE in Alzheimer disease (2024) · cites this paper as [131]

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: 58

  1. [1]Alderson TR Markley JL Biophysical characterization of alpha-synuclein and its controversial structure Intrinsic Disord Proteins 2013 1 18 39 10.4161/idp.26255 · DOI
  2. [4]Bergeron C Pollanen M Lewy bodies in Alzheimer disease–one or two diseases? Alzheimer Dis Assoc Disord 1989 3 197 204 10.1097/00002093-198900000-00002 2557056 · DOI
  3. [5]Beyer K Alpha-synuclein structure, posttranslational modification and alternative splicing as aggregation enhancers Acta Neuropathol 2006 112 237 251 10.1007/s00401-006-0104-6 16845533 · DOI
  4. [8]Bras J Guerreiro R Darwent L Parkkinen L Ansorge O Escott-Price V Hernandez DG Nalls MA Clark LN Honig LS Genetic analysis implicates APOE, SNCA and suggests lysosomal dysfunction in the etiology of dementia with Lewy bodies Hum Mol Genet 2014 23 6139 6146 10.1093/hmg/ddu334 24973356 PMC4222357 · DOI · Paper page
  5. [10]Cheung HH Liu X Canterel-Thouennon L Li L Edmonson C Rennert OM Telomerase protects werner syndrome lineage-specific stem cells from premature aging Stem Cell Reports 2014 2 534 546 10.1016/j.stemcr.2014.02.006 24749076 PMC3986587 · DOI · Paper page
  6. [13]Dickson DW Heckman MG Murray ME Soto AI Walton RL Diehl NN van Gerpen JA Uitti RJ Wszolek ZK Ertekin-Taner N APOE epsilon4 is associated with severity of Lewy body pathology independent of Alzheimer pathology Neurology 2018 91 e1182 e1195 10.1212/WNL.0000000000006212 30143564 PMC6161556 · DOI · Paper page
  7. [14]Donaghy PC McKeith IG The clinical characteristics of dementia with Lewy bodies and a consideration of prodromal diagnosis Alzheimers Res Ther 2014 6 46 10.1186/alzrt274 25484925 PMC4255387 · DOI
  8. [15]Fauvet B Mbefo MK Fares MB Desobry C Michael S Ardah MT Tsika E Coune P Prudent M Lion N alpha-Synuclein in central nervous system and from erythrocytes, mammalian cells, and Escherichia coli exists predominantly as disordered monomer J Biol Chem 2012 287 15345 15364 10.1074/jbc.M111.318949 22315227 PMC3346117 · DOI
  9. [18]Galasko D Saitoh T Xia Y Thal LJ Katzman R Hill LR Hansen L The apolipoprotein E allele epsilon 4 is overrepresented in patients with the Lewy body variant of Alzheimer's disease Neurology 1994 44 1950 1951 10.1212/WNL.44.10.1950 7936253 · DOI
  10. [19]Galkin M Priss A Topcheva O Yushchenko DA Shvadchak VV FRET-based assay for intracellular evaluation of alpha-synuclein aggregation inhibitors J Neurochem 2021 159 901 912 10.1111/jnc.15528 34687236 · DOI
  11. [20]Groveman BR Orru CD Hughson AG Raymond LD Zanusso G Ghetti B Campbell KJ Safar J Galasko D Caughey B Rapid and ultra-sensitive quantitation of disease-associated alpha-synuclein seeds in brain and cerebrospinal fluid by alphaSyn RT-QuIC Acta Neuropathol Commun 2018 6 7 10.1186/s40478-018-0508-2 29422107 PMC5806364 · DOI
  12. [21]Guerreiro R Ross OA Kun-Rodrigues C Hernandez DG Orme T Eicher JD Shepherd CE Parkkinen L Darwent L Heckman MG Investigating the genetic architecture of dementia with Lewy bodies: a two-stage genome-wide association study Lancet Neurol 2018 17 64 74 10.1016/S1474-4422(17)30400-3 29263008 PMC5805394 · DOI · Paper page
  13. [22]Guo T Zhang D Zeng Y Huang TY Xu H Zhao Y Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer's disease Mol Neurodegener 2020 15 40 10.1186/s13024-020-00391-7 32677986 PMC7364557 · DOI · Paper page
  14. [23]Hijaz BA Volpicelli-Daley LA Initiation and propagation of alpha-synuclein aggregation in the nervous system Mol Neurodegener 2020 15 19 10.1186/s13024-020-00368-6 32143659 PMC7060612 · DOI
  15. [24]Holmes BB Furman JL Mahan TE Yamasaki TR Mirbaha H Eades WC Belaygorod L Cairns NJ Holtzman DM Diamond MI Proteopathic tau seeding predicts tauopathy in vivo Proc Natl Acad Sci U S A 2014 111 E4376 4385 25261551 PMC4205609
  16. [25]Huang X Chen P Kaufer DI Troster AI Poole C Apolipoprotein E and dementia in Parkinson disease: a meta-analysis Arch Neurol 2006 63 189 193 10.1001/archneur.63.2.189 16476806 · DOI · Paper page
  17. [26]Irwin DJ White MT Toledo JB Xie SX Robinson JL Van Deerlin V Lee VM Leverenz JB Montine TJ Duda JE Neuropathologic substrates of Parkinson disease dementia Ann Neurol 2012 72 587 598 10.1002/ana.23659 23037886 PMC3484250 · DOI · Paper page
  18. [28]Jo E McLaurin J Yip CM St George-Hyslop P Fraser PE alpha-Synuclein membrane interactions and lipid specificity J Biol Chem 2000 275 34328 34334 10.1074/jbc.M004345200 10915790 · DOI
  19. [29]Josephs KA Whitwell JL Weigand SD Murray ME Tosakulwong N Liesinger AM Petrucelli L Senjem ML Knopman DS Boeve BF TDP-43 is a key player in the clinical features associated with Alzheimer's disease Acta Neuropathol 2014 127 811 824 10.1007/s00401-014-1269-z 24659241 PMC4172544 · DOI · Paper page
  20. [31]Kim R Park S Yoo D Jun JS Jeon B Impact of the apolipoprotein E epsilon4 allele on early Parkinson's disease progression Parkinsonism Relat Disord 2021 83 66 70 10.1016/j.parkreldis.2021.01.004 33484977 · DOI
  21. [32]Koga S Sekiya H Kondru N Ross OA Dickson DW Neuropathology and molecular diagnosis of Synucleinopathies Mol Neurodegener 2021 16 83 10.1186/s13024-021-00501-z 34922583 PMC8684287 · DOI
  22. [33]Kumar ST Jagannath S Francois C Vanderstichele H Stoops E Lashuel HA How specific are the conformation-specific alpha-synuclein antibodies? Characterization and validation of 16 alpha-synuclein conformation-specific antibodies using well-characterized preparations of alpha-synuclein monomers, fibrils and oligomers with distinct structures and morphology Neurobiol Dis 2020 146 105086 10.1016/j.nbd.2020.105086 32971232 · DOI
  23. [34]Kunkle BW Grenier-Boley B Sims R Bis JC Damotte V Naj AC Boland A Vronskaya M van der Lee SJ Amlie-Wolf A Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates Abeta, tau, immunity and lipid processing Nat Genet 2019 51 414 430 10.1038/s41588-019-0358-2 30820047 PMC6463297 · DOI · Paper page
  24. [35]Liu CC Yamazaki Y Heckman MG Martens YA Jia L Yamazaki A Diehl NN Zhao J Zhao N DeTure M Tau and apolipoprotein E modulate cerebrovascular tight junction integrity independent of cerebral amyloid angiopathy in Alzheimer's disease Alzheimers Dement 2020 16 1372 1383 10.1002/alz.12104 32827351 PMC8103951 · DOI
  25. [36]Liu G Peng J Liao Z Locascio JJ Corvol JC Zhu F Dong X Maple-Grodem J Campbell MC Elbaz A Genome-wide survival study identifies a novel synaptic locus and polygenic score for cognitive progression in Parkinson's disease Nat Genet 2021 53 787 793 10.1038/s41588-021-00847-6 33958783 PMC8459648 · DOI · Paper page
  26. [37]Lou X Kim J Hawk BJ Shin YK alpha-Synuclein may cross-bridge v-SNARE and acidic phospholipids to facilitate SNARE-dependent vesicle docking Biochem J 2017 474 2039 2049 10.1042/BCJ20170200 28495859 PMC5772654 · DOI
  27. [38]Mahul-Mellier AL Burtscher J Maharjan N Weerens L Croisier M Kuttler F Leleu M Knott GW Lashuel HA The process of Lewy body formation, rather than simply alpha-synuclein fibrillization, is one of the major drivers of neurodegeneration Proc Natl Acad Sci U S A 2020 117 4971 4982 10.1073/pnas.1913904117 32075919 PMC7060668 · DOI · Paper page
  28. [39]Man WK Tahirbegi B Vrettas MD Preet S Ying L Vendruscolo M De Simone A Fusco G The docking of synaptic vesicles on the presynaptic membrane induced by alpha-synuclein is modulated by lipid composition Nat Commun 2021 12 927 10.1038/s41467-021-21027-4 33568632 PMC7876145 · DOI
  29. [40]Manne S Kondru N Hepker M Jin H Anantharam V Lewis M Huang X Kanthasamy A Kanthasamy AG Ultrasensitive detection of aggregated alpha-synuclein in glial cells, human cerebrospinal fluid, and brain tissue using the RT-QuIC assay: new high-throughput neuroimmune biomarker assay for Parkinsonian disorders J Neuroimmune Pharmacol 2019 14 423 435 10.1007/s11481-019-09835-4 30706414 PMC6669119 · DOI
  30. [41]Manne S Kondru N Jin H Anantharam V Huang X Kanthasamy A Kanthasamy AG alpha-Synuclein real-time quaking-induced conversion in the submandibular glands of Parkinson's disease patients Mov Disord 2020 35 268 278 10.1002/mds.27907 31758740 PMC7102508 · DOI
  31. [42]Manne S Kondru N Jin H Serrano GE Anantharam V Kanthasamy A Adler CH Beach TG Kanthasamy AG Blinded RT-QuIC analysis of alpha-synuclein biomarker in skin tissue from parkinson's disease patients Mov Disord 2020 35 2230 2239 10.1002/mds.28242 32960470 PMC7749035 · DOI
  32. [43]McKeith IG Boeve BF Dickson DW Halliday G Taylor JP Weintraub D Aarsland D Galvin J Attems J Ballard CG Diagnosis and management of dementia with Lewy bodies: Fourth consensus report of the DLB Consortium Neurology 2017 89 88 100 10.1212/WNL.0000000000004058 28592453 PMC5496518 · DOI · Paper page
  33. [44]Meade RM Fairlie DP Mason JM Alpha-synuclein structure and Parkinson's disease - lessons and emerging principles Mol Neurodegener 2019 14 29 10.1186/s13024-019-0329-1 31331359 PMC6647174 · DOI
  34. [45]Meneses A Koga S O'Leary J Dickson DW Bu G Zhao N TDP-43 Pathology in Alzheimer's Disease Mol Neurodegener 2021 16 84 10.1186/s13024-021-00503-x 34930382 PMC8691026 · DOI
  35. [46]Norris EH Giasson BI Lee VM Alpha-synuclein: normal function and role in neurodegenerative diseases Curr Top Dev Biol 2004 60 17 54 10.1016/S0070-2153(04)60002-0 15094295 · DOI
  36. [47]Olichney JM Galasko D Salmon DP Hofstetter CR Hansen LA Katzman R Thal LJ Cognitive decline is faster in Lewy body variant than in Alzheimer's disease Neurology 1998 51 351 357 10.1212/WNL.51.2.351 9710002 · DOI
  37. [48]Papapetropoulos S Farrer MJ Stone JT Milkovic NM Ross OA Calvo L McQuorquodale D Mash DC Phenotypic associations of tau and ApoE in Parkinson's disease Neurosci Lett 2007 414 141 144 10.1016/j.neulet.2006.12.008 17204369 · DOI
  38. [49]Paslawski W Zareba-Paslawska J Zhang X Holzl K Wadensten H Shariatgorji M Janelidze S Hansson O Forsgren L Andren PE alpha-synuclein-lipoprotein interactions and elevated ApoE level in cerebrospinal fluid from Parkinson's disease patients Proc Natl Acad Sci U S A 2019 116 15226 15235 10.1073/pnas.1821409116 31270237 PMC6660770 · DOI
  39. [51]Robinson JL Lee EB Xie SX Rennert L Suh E Bredenberg C Caswell C Van Deerlin VM Yan N Yousef A Neurodegenerative disease concomitant proteinopathies are prevalent, age-related and APOE4-associated Brain 2018 141 2181 2193 10.1093/brain/awy146 29878075 PMC6022546 · DOI · Paper page
  40. [52]Rossi M Candelise N Baiardi S Capellari S Giannini G Orru CD Antelmi E Mammana A Hughson AG Calandra-Buonaura G Ultrasensitive RT-QuIC assay with high sensitivity and specificity for Lewy body-associated synucleinopathies Acta Neuropathol 2020 140 49 62 10.1007/s00401-020-02160-8 32342188 PMC7299922 · DOI
  41. [53]Santos OA Pedraza O Lucas JA Duara R Greig-Custo MT Hanna Al-Shaikh FS Liesinger AM Bieniek KF Hinkle KM Lesser ER Ethnoracial differences in Alzheimer's disease from the florida autopsied multi-ethnic (FLAME) cohort Alzheimers Dement 2019 15 635 643 10.1016/j.jalz.2018.12.013 30792090 PMC6511501 · DOI
  42. [54]Shahnawaz M Mukherjee A Pritzkow S Mendez N Rabadia P Liu X Hu B Schmeichel A Singer W Wu G Discriminating alpha-synuclein strains in Parkinson's disease and multiple system atrophy Nature 2020 578 273 277 10.1038/s41586-020-1984-7 32025029 PMC7066875 · DOI · Paper page
  43. [55]Singleton AB Wharton A O'Brien KK Walker MP McKeith IG Ballard CG O'Brien J Perry RH Ince PG Edwardson JA Clinical and neuropathological correlates of apolipoprotein E genotype in dementia with Lewy bodies Dement Geriatr Cogn Disord 2002 14 167 175 10.1159/000066022 12411758 · DOI
  44. [56]Tan MMX Lawton MA Jabbari E Reynolds RH Iwaki H Blauwendraat C Kanavou S Pollard MI Hubbard L Malek N Genome-wide association studies of cognitive and motor progression in Parkinson's disease Mov Disord 2021 36 424 433 10.1002/mds.28342 33111402 PMC9053517 · DOI
  45. [57]Thal DR Rub U Orantes M Braak H Phases of A beta-deposition in the human brain and its relevance for the development of AD Neurology 2002 58 1791 1800 10.1212/WNL.58.12.1791 12084879 · DOI · Paper page
  46. [58]Theillet FX Binolfi A Bekei B Martorana A Rose HM Stuiver M Verzini S Lorenz D van Rossum M Goldfarb D Structural disorder of monomeric alpha-synuclein persists in mammalian cells Nature 2016 530 45 50 10.1038/nature16531 26808899 · DOI
  47. [59]Tsuang D Leverenz JB Lopez OL Hamilton RL Bennett DA Schneider JA Buchman AS Larson EB Crane PK Kaye JA APOE epsilon4 increases risk for dementia in pure synucleinopathies JAMA Neurol 2013 70 223 228 10.1001/jamaneurol.2013.600 23407718 PMC3580799 · DOI · Paper page
  48. [60]Tsuang DW Wilson RK Lopez OL Luedecking-Zimmer EK Leverenz JB DeKosky ST Kamboh MI Hamilton RL Genetic association between the APOE*4 allele and Lewy bodies in Alzheimer disease Neurology 2005 64 509 513 10.1212/01.WNL.0000150892.81839.D1 15699383 PMC1487185 · DOI
  49. [61]Twohig D Nielsen HM alpha-synuclein in the pathophysiology of Alzheimer's disease Mol Neurodegener 2019 14 23 10.1186/s13024-019-0320-x 31186026 PMC6558879 · DOI · Paper page
  50. [62]Wang W Perovic I Chittuluru J Kaganovich A Nguyen LT Liao J Auclair JR Johnson D Landeru A Simorellis AK A soluble alpha-synuclein construct forms a dynamic tetramer Proc Natl Acad Sci U S A 2011 108 17797 17802 10.1073/pnas.1113260108 22006323 PMC3203798 · DOI · Paper page
  51. [63]Wood SJ Wypych J Steavenson S Louis JC Citron M Biere AL alpha-synuclein fibrillogenesis is nucleation-dependent. Implications for the pathogenesis of Parkinson's disease J Biol Chem 1999 274 19509 19512 10.1074/jbc.274.28.19509 10391881 · DOI
  52. [64]Yamasaki TR Holmes BB Furman JL Dhavale DD Su BW Song ES Cairns NJ Kotzbauer PT Diamond MI Parkinson's disease and multiple system atrophy have distinct alpha-synuclein seed characteristics J Biol Chem 2019 294 1045 1058 10.1074/jbc.RA118.004471 30478174 PMC6341389 · DOI
  53. [65]Yamazaki Y Shinohara M Shinohara M Yamazaki A Murray ME Liesinger AM Heckman MG Lesser ER Parisi JE Petersen RC Selective loss of cortical endothelial tight junction proteins during Alzheimer's disease progression Brain 2019 142 1077 1092 10.1093/brain/awz011 30770921 PMC6439325 · DOI · Paper page
  54. [66]Yamazaki Y Zhao N Caulfield TR Liu CC Bu G Apolipoprotein E and Alzheimer disease: pathobiology and targeting strategies Nat Rev Neurol 2019 15 501 518 10.1038/s41582-019-0228-7 31367008 PMC7055192 · DOI · Paper page
  55. [67]Zhao J Davis MD Martens YA Shinohara M Graff-Radford NR Younkin SG Wszolek ZK Kanekiyo T Bu G APOE epsilon4/epsilon4 diminishes neurotrophic function of human iPSC-derived astrocytes Hum Mol Genet 2017 26 2690 2700 10.1093/hmg/ddx155 28444230 PMC5886091 · DOI · Paper page
  56. [68]Zhao J Fu Y Liu CC Shinohara M Nielsen HM Dong Q Kanekiyo T Bu G Retinoic acid isomers facilitate apolipoprotein E production and lipidation in astrocytes through the retinoid X receptor/retinoic acid receptor pathway J Biol Chem 2014 289 11282 11292 10.1074/jbc.M113.526095 24599963 PMC4036266 · DOI
  57. [69]Zhao J Fu Y Yamazaki Y Ren Y Davis MD Liu CC Lu W Wang X Chen K Cherukuri Y APOE4 exacerbates synapse loss and neurodegeneration in Alzheimer's disease patient iPSC-derived cerebral organoids Nat Commun 2020 11 5540 10.1038/s41467-020-19264-0 33139712 PMC7608683 · DOI · Paper page
  58. [71]Zhao N Liu CC Qiao W Bu G Apolipoprotein E, receptors, and modulation of Alzheimer's disease Biol Psychiatry 2018 83 347 357 10.1016/j.biopsych.2017.03.003 28434655 PMC5599322 · DOI · Paper page

Cited by

Sorted by citations

Authors
Jin, Y., Li, F., Sonoustoun, B., Kondru, N. C., Martens, Y. A., Qiao, W., Heckman, M. G., Ikezu, T. C., Li, Z., Burgess, J. D., Amerna, D., O’Leary, J., DeTure, M. A., Zhao, J., McLean, P. J., Dickson, D. W., Ross, O. A., Bu, G., & Zhao, N.
Affiliations
  • Mayo Clinic (US)
  • Mayo Clinic in Florida (US)
Corresponding author
  • Bu, Guojun
  • Zhao, Na
ORCID
Venue
Acta Neuropathologica
Publisher
Springer Science and Business Media LLC
Published
2022-04-26
Volume
143
Issue
6
Pages
641-662
ISSN
  • 0001-6322 (ISSN-L)
  • 1432-0533
DOI
10.1007/s00401-022-02421-8
PMC
PMC9107450
OpenAlex
W4224504085
Cited by
69
References
5
Citations by year
2026: 14 · 2025: 17 · 2024: 15 · 2023: 15 · 2022: 8
FWCI
8.50
Type
journal article
Language
en
Open access
Licence
Locations
  • Acta Neuropathologica (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
Funders
  • Mayo Alzheimer’s Disease Research Center Developmental Grant
  • National Institute of Neurological Disorders and Stroke (U54NS110435)
  • National Institute on Aging (U19AG069701)
  • Ted Turner and Family
  • The Little Family Foundation
  • The Mayo Clinic Center of Indiviudualized Medicine and an MSA Coalition award
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
APOE ε4, alpha-synuclein, seeding activity, Lewy body pathology, Alzheimer's disease, dementia with Lewy bodies, neurotoxicity, amyloid-beta, tau protein, protein aggregation, RT-QuIC, iPSC-derived neurons, genetic risk factors
MeSH terms
Alzheimer Disease, Apolipoproteins E, Humans, Lewy Bodies, tau Proteins, Neurotoxicity Syndromes, Lewy Body Disease, alpha-Synuclein, Apolipoprotein E4, Genome-Wide Association Study, Induced Pluripotent Stem Cells

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