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,

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

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

Creative Commons Attribution-Noncommercial 4.0 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

Included in

Diseases Commons

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