Maternal fish-oil supplementation reduces presenilin 1 level and the amyloid-beta burden in adult 5xFAD offspring without major changes in brain fatty acids

Abstract

Omega-3 fatty acid interventions show potential benefits in Alzheimer’s disease (AD) when initiated during its early stages. This study investigated whether maternal diet supplemented with omega-3-rich fish oil (FO) could delay or reduce amyloid beta (Aβ) formation, a key feature of AD, in 5xFAD transgenic offspring. Dams received FO during mating, pregnancy, and lactation. Brain tissues from female offspring were collected at 2 and 6 months of age. The findings indicated a shift in amyloid precursor protein processing, evidenced by increased soluble amyloid precursor protein α (sAPPα) levels, suggesting a transition from amyloidogenic to non-amyloidogenic pathway. FO influenced the expression of presenilin 1 and 2 but did not impact Aβ levels in 2-month-old mice. However, FO reduced the Aβ burden in the brains of 6-month-old animals. Lipidomic analysis revealed that 5xFAD mice have unimpaired omega-3 acquisition during gestation and lactation in comparison to non-transgenic littermates. However, a response to FO supplementation was found in non-transgenic offspring only, indicating that alterations in brain lipids are not the primary mechanism of FO-induced Aβ decline in 5xFAD. In conclusion, FO did not prevent or delay amyloid pathology in genetically predisposed animals but did mitigate its progression, suggesting mechanisms that warrant further investigation.

Keywords

• fish oil
• maternal treatment
• brain fatty acids
• omega-3
• alzheimer's disease