A Diet Enriched with the Omega-3 Fatty Acid Docosahexaenoic Acid Reduces Amyloid Burden in an Aged Alzheimer Mouse Model

TLDR

Epidemiological studies link higher intake of omega‑3 DHA to lower Alzheimer’s disease risk, yet AD patients have reduced DHA levels in serum and brain. The study aimed to determine whether dietary DHA affects amyloid precursor protein processing and amyloid burden in aged APPsw mice. Aged Tg2576 mice (17–19 mo) were fed control (0.09 % DHA), low‑DHA (0 %), or high‑DHA (0.6 %) chow until 22.5 mo to assess effects on amyloid pathology. High‑DHA chow lowered cortical insoluble Aβ by >70 %, reduced Aβ42, cut plaque burden by 40 %, and decreased APP processing, supporting DHA’s protective role against amyloid accumulation.

Abstract

Epidemiological studies suggest that increased intake of the omega-3 (n-3) polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA) is associated with reduced risk of Alzheimer's disease (AD). DHA levels are lower in serum and brains of AD patients, which could result from low dietary intake and/or PUFA oxidation. Because effects of DHA on Alzheimer pathogenesis, particularly on amyloidosis, are unknown, we used the APPsw (Tg2576) transgenic mouse model to evaluate the impact of dietary DHA on amyloid precursor protein (APP) processing and amyloid burden. Aged animals (17-19 months old) were placed in one of three groups until 22.5 months of age: control (0.09% DHA), low-DHA (0%), or high-DHA (0.6%) chow. β-Amyloid (Aβ) ELISA of the detergent-insoluble extract of cortical homogenates showed that DHA-enriched diets significantly reduced total Aβ by >70% when compared with low-DHA or control chow diets. Dietary DHA also decreased Aβ42 levels below those seen with control chow. Image analysis of brain sections with an antibody against Aβ (amino acids 1-13) revealed that overall plaque burden was significantly reduced by 40.3%, with the largest reductions (40-50%) in the hippocampus and parietal cortex. DHA modulated APP processing by decreasing both α- and β-APP C-terminal fragment products and full-length APP. BACE1 (β-secretase activity of the β-site APP-cleaving enzyme), ApoE (apolipoprotein E), and transthyretin gene expression were unchanged with the high-DHA diet. Together, these results suggest that dietary DHA could be protective against β-amyloid production, accumulation, and potential downstream toxicity.