Document Type
Journal Article
Publication Title
Alzheimer's & Dementia
Publisher
Wiley
School
School of Medical and Health Sciences / Centre for Precision Health
RAS ID
43277
Funders
Funding information : https://doi.org/10.1002/alz.12538 National Health and Medical Research Council Edith Cowan University
Grant Number
NHMRC Number : 1101320, 1157607, 1197190,
Grant Link
http://purl.org/au-research/grants/nhmrc/1101320
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.
DOI
10.1002/alz.12538
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License
Research Themes
Health
Priority Areas
Multidisciplinary biological approaches to personalised disease diagnosis, prognosis and management
Comments
Wang, T., Huynh, K., Giles, C., Mellett, N. A., Duong, T., Nguyen, A., . . . Meikle, P. J. (2022). APOE ε2 resilience for Alzheimer's disease is mediated by plasma lipid species: Analysis of three independent cohort studies. Alzheimer's & Dementia. Advance online publication.
https://doi.org/10.1002/alz.12538