Omega-3 polyunsaturated fatty acids promote brain-to-blood clearance of -Amyloid in a mouse model with Alzheimer's disease

Amyloid-beta (A beta) plaques is one of the typical pathological hallmark of Alzheimer disease (AD). Accumulating evidence suggests that the imbalance between A beta production and clearance leads to extracellular A beta accumulation in the brain. It is reported that the blood-brain barrier (BBB) transport plays a predominant role in A beta clearance from brain to blood. In the present study, we investigated dynamic alterations of BBB transport function in the early disease stage of AD using APPswe/PS1dE9 C57BL/6J (APP/PS1) transgenic mice. Our results showed that the expression of lipoprotein receptor-related protein 1 (LRP-1), a main efflux transporter of BBB, started to decrease at the age of 4 months old. Interestingly, supplementing with fish oil which is rich in omega-3 polyunsaturated fatty acids (PUFAs) significantly enhanced the expression level of LRP-1 and promoted A beta clearance from the bran to circulation, as revealed by reduced soluble/insoluble A beta levels and senile plaques in the brain parenchyma and a corresponding increase of A beta levels in plasma. Besides, fish oil supplement significantly inhibited the NF-kappa B activation, reduced the expression of interleukin-1 beta and tumor necrosis factor-alpha, and suppressed the glial activation in APP/PS1 mice. The results of the study provide evidence that BBB transport function could be impaired at a very early disease stage, which might contribute to A beta pathological accumulation in AD, and omega-3 PUFAs intervention could be an effective strategy for the prevention of the progression of AD through promoting A beta clearance from brain-to-blood.