The interactive impact of sex and APOE genotype on post‐mortem brain fatty acids profile in Alzheimer’s Disease, Results from the UK BrainBank.

Abstract

AbstractBackgroundTwo‐thirds of Alzheimer’s Disease (AD) patients are women, with the risk becoming higher if carrying the APOE4 genotype. Omega‐3 fatty acids status is associated with reduced risk of AD. Little is known about the interactive impact of sex and APOE genotype on brain fatty acids status. In this study, fatty acids were measured in post‐mortem brain tissue of AD patients and stratified according to sex and APOE genotype.MethodFatty acids were extracted from the hippocampus and frontal cortex of AD cases (n = 25, 11 are women) and controls (n = 25, 12 are women) using Folch method (from total lipids). Fatty acids were analysed using gas chromatography and flame ionization detection (GC‐FID). Samples were requested and granted from the UK Brain Bank. Adjustment for age and post‐mortem delay was done.ResultArachidonic acid (ARA) and n‐6DPA were higher in APOE4 women with AD compared to control (P‐Disease*sex*APOE = 0.01 and <0.001 respectively).These results were more evident in the hippocampus than the frontal cortex. n‐3DPA/ARA ratio (indicator of inflammatory status) was significantly higher in APOE4 women control compared to AD in both the hippocampus and frontal cortex (P‐disease*sex*APOE = 0.028 and <0.001 respectively). Similar trends were observed for EPA/ARA ratio. There was no impact of sex or APOE on BRAAK stage.ConclusionAPOE4 women with AD show a pro‐inflammatory brain fatty acid profile compared to controls, with increased n‐6 PUFAs (ARA and DPA) and reduced n‐3DPA/ARA ratios. Further extraction and analysis of fatty acids‐derived oxylipins and SPMs will be carried out.