APOE ε2 resilience for Alzheimer's disease is mediated by plasma lipid species: Analysis of three independent cohort studies. Issue 11 (25th January 2022)

• Record Type: Journal Article
• Authors: Wang, Tingting; Huynh, Kevin; Giles, Corey; Mellett, Natalie A; Duong, Thy; Nguyen, Anh; Lim, Wei Ling Florence; Smith, Alex AT; Olshansky, Gavriel; Cadby, Gemma; Hung, Joseph; Hui, Jennie; Beilby, John; Watts, Gerald F; Chatterjee, Pratishtha; Martins, Ian; Laws, Simon M; Bush, Ashley I; Rowe, Christopher C; Villemagne, Victor L; Ames, David; Masters, Colin L; Taddei, Kevin; Doré, Vincent; Fripp, Jürgen; Arnold, Matthias; Kastenmüller, Gabi; Nho, Kwangsik; Saykin, Andrew J; Baillie, Rebecca; Han, Xianlin; Martins, Ralph N; Moses, Eric K; Kaddurah‐Daouk, Rima; Meikle, Peter J;
• Is Part Of: Alzheimer's & dementia. Volume 18:Issue 11(2022)
• Page Start: 2151
• Page End: 2166
• Publication Date: 2022-01-25
• Subjects: APOE ε2 -- APOE ε4 -- Alzheimer's disease -- lipidomics -- lipid species -- mass spectrometry; Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.12538
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: 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.