The protective role of endogenous n-3 polyunsaturated fatty acids in Tau Alzheimer's disease mouse model

Objectives: The role of n-3 polyunsaturated fatty acid (PUFA) as the main docosahexaenoic acid (DHA) in Alzheimer's disease (AD) remains controversial. Our study aimed to provide detailed information about the role of endogenous n-3 PUFAs in AD. Methods: Here, we generated a fat-1/tau transgenic mouse AD model by crossing female tau mice with male fat-1 mice to exclude confounding variables associated with the benefit of a DHA diet in these AD mice models. PUFAs presented in these AD models were detected by gas chromatography, and the role of endogenous n-3 PUFAs was assessed by lifespan survival assay, behavioral, pathologic, and molecular biology testing as well as imaging of cerebral vasculature. Results: Endogenous n-3 PUFAs were shown to improve the memory and learning ability of AD mice. One possible reason for this improvement is the reduced formation of neurotrophic factors (NFTs) and A beta amyloid plaques which usually damage hippocampal neurons. Additionally, endogenous n-3 PUFAs were demonstrated to protect cerebral vascular of AD mice, thereby increasing brain metabolism. Besides, endogenous n-3 PUFAs were observed to extend of the overall survival of tau mouse models. Conclusion: Endogenous n-3 PUFAs delayed the onset of Alzheimer's disease caused by tau protein dysfunction, alleviating related symptoms and significantly prolonging survival in vivo.