APOE ε4 alters docosahexaenoic acid associations with preclinical markers of Alzheimer disease

Gillian Coughlan, Min Lim, Ryan Larsen, David White, Rachel Gillings, Michael Irvine, Andrew Scholey, Neal Cohen, Cristina Legido Quigley, Michael Hornberger, Anne-Marie Minihane

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Docosahexaenoic acid (DHA) is the main long chain omega-3 polyunsaturated fatty acids in the brain and accounts for 30% to 40% of fatty acids in the grey matter of the human cortex. Although the influence of DHA on memory function is widely researched, its association with brain volumes is under investigated and its association with spatial navigation is virtually unknown. This is despite the fact that spatial navigation deficits are a new cognitive fingerprint for symptomatic and asymptomatic Alzheimer’s disease (AD). We investigated the relationship between DHA levels and the major structural and cognitive markers of preclinical AD, namely hippocampal volume, entorhinal volume, and spatial navigation ability. Fifty-three cognitively normal adults underwent volumetric magnetic resonance imaging, measurements of serum DHA (including serum lysophosphatidylcholine DHA (LPC DHA)) and APOE ε4 genotyping. Relative regional brain volumes were calculated and linear regression models were fitted to examine DHA associations with brain volume. APOE genotype modulated serum DHA associations with entorhinal cortex volume and hippocampal volume. Linear models showed that greater serum DHA was associated with increased entorhinal cortex volume, but not hippocampal volume, in APOΕ ε4 non-carriers. APOE also interacted with serum LPC DHA to predict hippocampal volume. After testing interactions between DHA and APOE ε4 on brain volume, we investigated whether DHA and APOE interact to predict spatial navigation performance on a novel virtual reality diagnostic test for AD in an independent population of APOE genotyped adults (n = 46). Crucially, the APOE genotype modulated DHA associations with spatial navigation performance, showing that DHA was inversely associated with path integration in APOE ε4 carriers only. Interventions aiming to increase DHA status to protect against cognitive decline must consider APOE ε4 carrier status, and focus on higher doses of supplementary DHA to ensure adequate brain delivery.
Original languageEnglish
Article numberfcab085
JournalBrain Communications
Issue number2
Early online date11 May 2021
Publication statusPublished - 2021

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