Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is accompanied by memory deficits and neuropsychiatric dysfunction.

Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have seemly therapeutic potential in AD, but the benefit of n-3 PUFAs is still in debate. Here, we report that transgenic mice carry the fat-1 gene to encode n-3 desaturase from Caenorhabditis elegans, which increases endogenous n-3 PUFAs by converting n-6 PUFAs to n-3 PUFAs. The study aims to evaluate the protective effects of endogenous n-3 PUFAs on cognitive and behavioral deficits of amyloid precursor protein (APP) mice.

We fed APP, APP/fat-1 and fat-1 mice with n-6 PUFAs rich diet. Brain tissues were collected at 3, 6 and 9months for fattyacid and gene expression analysis, histology and protein assays. Morris Water Maze Test, open field test and elevated plus maze test were performed to measure the behavior capability.

From the results, the expression of fat-1 transgene increased cortical n-3:n-6 PUFAs ratio and n-3 PUFAs concentrations, and improved cognitive impairment and neuropsychological symptoms in AD. Sensorimotor dysfunction and cognitive deficits in AD were significantly less severe in APP/fat-1 mice with endogenous n-3 PUFAs than in APP mice controls.

The protection against disturbance of spontaneous motor activity and cognitive deficits in AD was strongly correlated with increased n-3: n-6 PUFAs ratio and endogenous n-3 PUFAs, reduced APP generation, inhibited amyloid β peptide aggregation, suppressed nuclear factor-kappa B and astroglia activation, and reduced death of neurons in the cortex of APP/fat-1 mice compared with APP mice controls.

In conclusion, our study demonstrates that an available medication with the maintenance of enriched n-3 PUFAs in the brain could slow down cognitive decline and prevent neuropsychological disorder in AD.