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Wang, T.* ; Huynh, K.* ; Giles, C.* ; Mellett, N.A.* ; Duong, T.* ; Nguyen, A.* ; Lim, W.L.F.* ; Smith, A.A.T.* ; Olshansky, G.* ; Cadby, G.* ; Hung, J.* ; Hui, J.* ; Beilby, J.* ; Watts, G.F.* ; Chatterjee, P.* ; Martins, I.* ; Laws, S.M.* ; Bush, A.I.* ; Rowe, C.C.* ; Villemagne, V.L.* ; Ames, D.* ; Masters, C.L.* ; Taddei, K.* ; Doré, V.* ; Fripp, J.* ; Arnold, M. ; Kastenmüller, G. ; Nho, K.* ; Saykin, A.J.* ; Baillie, R.* ; Han, X.* ; Martins, R.N.* ; Moses, E.K.* ; Kaddurah-Daouk, R.* ; Meikle, P.J.*

APOE ε2 resilience for Alzheimer's disease is mediated by plasma lipid species: Analysis of three independent cohort studies.

Alzheimers Dement. 18, 2151-2166 (2022)
Publ. Version/Full Text Research data DOI PMC
Open Access Hybrid
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Introduction: The apolipoprotein E (APOE) genotype is the strongest genetic risk factor for late-onset Alzheimer's disease. However, its effect on lipid metabolic pathways, and their mediating effect on disease risk, is poorly understood. Methods: We performed lipidomic analysis on three independent cohorts (the Australian Imaging, Biomarkers and Lifestyle [AIBL] flagship study, n = 1087; the Alzheimer's Disease Neuroimaging Initiative [ADNI] 1 study, n = 819; and the Busselton Health Study [BHS], n = 4384), and we defined associations between APOE ε2 and ε4 and 569 plasma/serum lipid species. Mediation analysis defined the proportion of the treatment effect of the APOE genotype mediated by plasma/serum lipid species. Results: A total of 237 and 104 lipid species were associated with APOE ε2 and ε4, respectively. Of these 68 (ε2) and 24 (ε4) were associated with prevalent Alzheimer's disease. Individual lipid species or lipidomic models of APOE genotypes mediated up to 30% and 10% of APOE ε2 and ε4 treatment effect, respectively. Discussion: Plasma lipid species mediate the treatment effect of APOE genotypes on Alzheimer's disease and as such represent a potential therapeutic target.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Apoe Epsilon 2 ; Apoe Epsilon 4 ; Alzheimer's Disease ; Lipidomics ; Lipid Species ; Mass Spectrometry; Density-lipoprotein Cholesterol; Coronary-artery-disease; Natural Alkylglycerols; Cognitive Decline; Risk; Association; Dementia; Individuals; Trafficking; Degradation
Language english
Publication Year 2022
HGF-reported in Year 2022
ISSN (print) / ISBN 1552-5260
e-ISSN 1552-5279
Journal Alzheimer's & Dementia
Quellenangaben Volume: 18, Issue: 11, Pages: 2151-2166 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place New York, NY [u.a.]
Reviewing status Peer reviewed
Institute(s) Institute of Computational Biology (ICB)
POF-Topic(s) 30205 - Bioengineering and Digital Health
Research field(s) Enabling and Novel Technologies
PSP Element(s) G-503891-001
Grants Austin Health, and CogState Ltd.
Dementia Australia Research Foundation Scholarship
Victorian Government's Operational Infrastructure Support Program
Commonwealth. Scientific Industrial and Research Organization [CSIRO]
Edith CowanUniversity [ECU]
Mental Health Research institute [MHRI]
National Ageing Research Institute [NARI]
Dementia Collaborative Research Centre (DCRC2)
Science and Industry Endowment Fund (SIEF)
Cooperative Research Centre (CRC)
Qatar National Research Fund
NLM
NIA
NIH
National Health and Medical Research Council (NHMRC) of Australia
DOI 10.1002/alz.12538
WOS ID WOS:000746537300001
Scopus ID 85123489503
PubMed ID 35077012
Erfassungsdatum 2022-02-08
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