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.