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Omega-3 fatty acids and Alzheimer's disease-related brain biomarkers in older adults enriched for preclinical Alzheimer's disease

Danielle N. Christifano, Emma Kelly, S. Sands, R. Honea, Jill K. Morris, Jeffrey M. Burns, Matthew K. Taylor

Prostaglandins, Leukotrienes and Essential Fatty Acids, 2026

104 participants

Abstract

BACKGROUND

Preclinical and limited human data suggest long-chain omega-3 fatty acids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), may be protective of brain volume and amyloid-beta (Aβ) accumulation, hallmarks of Alzheimer's disease (AD), which may be modulated by Apolipoprotein E ε4 (APOE4) carriage.

METHODS

This cross-sectional study was conducted using baseline data from a clinical trial at the University of Kansas Medical Center that included cognitively normal older adults, enriched for preclinical AD. We investigated serum DHA+EPA's (% total triacylglycerol fatty acids) relationship with MRI-derived gray matter volume and PET-derived Aβ burden (Florbetapir F18) overall and by APOE4 carriage status.

RESULTS

Among all participants (n = 104, 67.3% female, 69.2% preclinical AD, 44.2% APOE4), higher DHA+EPA was related to larger gray matter volume in a left precuneus/postcentral gyrus cluster, with similar relationships between APOE4 carriers and non-carriers. Higher DHA+EPA was also related to lower brain Aβ in the frontoparietal cortex, bilaterally. In APOE sensitivity analyses, higher DHA+EPA was related to lower global and AD-related regional brain Aβ among APOE4 carriers .

CONCLUSIONS

Higher DHA+EPA was associated with larger gray matter volume and lower Aβ in AD-susceptible regions, especially among APOE4 carriers. These findings are consistent with the hypothesis that omega-3 fatty acids influence brain volume and Aβ. Well-designed DHA+EPA…

How strong is the evidence?

Evidence Hub reads this as a cross-sectional, done in people. Its evidence level is 4 of 5 (Low · observational). Observational designs can show an association but not prove cause. Reported size: 104 participants or records.

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