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

Abstract

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 Aβ 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.

Keywords:

• Alzheimer’s disease
• tau protein
• transgenic mouse models
• n-3 PUFAs
• survival rate
• cerebral vascular

Acknowledgments

Fat-1 mice were generously provided by Dr. Jing X. Kang. All mice were fed and housed at the Guangdong Laboratory Animal Monitoring Institute (GDLAMI) SPF (specific pathogen free) animal laboratory. This study was approved by the Institution Animal Care and Use Committee at the GDLAMI.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [grant number 31772549] and Science and Technology Planning Project of Guangdong Province of China [grant number 2017A070702001].