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

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dc.contributor.authorWang, Tingting
dc.contributor.authorHuynh, Kevin
dc.contributor.authorGiles, Corey
dc.contributor.authorMellett, Natalie A.
dc.contributor.authorDuong, Thy
dc.contributor.authorNguyen, Anh
dc.contributor.authorLim, Wei Ling Florence
dc.contributor.authorSmith, Alex At
dc.contributor.authorOlshansky, Gavriel
dc.contributor.authorCadby, Gemma
dc.contributor.authorHung, Joseph
dc.contributor.authorHui, Jennie
dc.contributor.authorBeilby, John
dc.contributor.authorWatts, Gerald F.
dc.contributor.authorChatterjee, Pratishtha
dc.contributor.authorMartins, Ian
dc.contributor.authorLaws, Simon M.
dc.contributor.authorBush, Ashley I.
dc.contributor.authorRowe, Christopher C.
dc.contributor.authorVillemagne, Victor L.
dc.contributor.authorAmes, David
dc.contributor.authorMasters, Colin L.
dc.contributor.authorTaddei, Kevin
dc.contributor.authorDoré, Vincent
dc.contributor.authorFripp, Jürgen
dc.contributor.authorArnold, Matthias
dc.contributor.authorKastenmüller, Gabi
dc.contributor.authorNho, Kwangsik
dc.contributor.authorSaykin, Andrew J.
dc.contributor.authorBaillie, Rebecca
dc.contributor.authorHan, Xianlin
dc.contributor.authorMartins, Ralph N.
dc.contributor.authorMoses, Eric K.
dc.contributor.authorKaddurah-Daouk, Rima
dc.contributor.authorMeikle, Peter J.
dc.contributor.departmentRadiology and Imaging Sciences, School of Medicine
dc.date.accessioned2023-10-10T14:34:46Z
dc.date.available2023-10-10T14:34:46Z
dc.date.issued2022
dc.description.abstractIntroduction: 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.
dc.eprint.versionFinal published version
dc.identifier.citationWang T, Huynh K, Giles C, et al. APOE ε2 resilience for Alzheimer's disease is mediated by plasma lipid species: Analysis of three independent cohort studies. Alzheimers Dement. 2022;18(11):2151-2166. doi:10.1002/alz.12538
dc.identifier.urihttps://hdl.handle.net/1805/36227
dc.language.isoen_US
dc.publisherWiley
dc.relation.isversionof10.1002/alz.12538
dc.relation.journalAlzheimer's & Dementia
dc.rightsAttribution-NonCommercial 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/
dc.sourcePMC
dc.subjectAPOE ε2
dc.subjectAPOE ε4
dc.subjectAlzheimer's disease
dc.subjectLipidomics
dc.subjectLipid species
dc.subjectMass spectrometry
dc.titleAPOE ε2 resilience for Alzheimer's disease is mediated by plasma lipid species: Analysis of three independent cohort studies
dc.typeArticle
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