Cerebral inoculation of human A53T α-synuclein reduces spatial memory decline and amyloid-β aggregation in APP/PS1 transgenic mice of Alzheimer's disease

Amyloid-beta (A beta) peptide and a-synuclein (alpha-syn) are major components of senile plaques in Alzheimer's disease (AD) and Lewy bodies in Parkinson's disease (PD), respectively. Co-occurrence of A beta and alpha-syn in the senile brains of AD and LB diseases suggests interactions between the two proteins. However, the significance of the overlapping deposition, especially the effects of alpha-syn on the A beta aggregation, still remains to be clarified. In the present study, we investigated the effects of alpha-syn pre-formed fibrils (PFFs) injection on the cognitive behaviors and A beta deposition in the brain of APP/PS1 transgenic AD mice by using Morris water maze (MWM) test, immunohistochemistry and western blot techniques. We found that APP/PS1 transgenic mice exhibited an obvious elevation in the alpha-syn load, as well as A beta deposition in the brain compared with wild type of C57 BL littermates. 5 months after cerebral injection of exogenous alpha-syn, MWM tests showed an alleviation in cognitive impairments in APP/PS1 mice; western blot and immunohistochemistry experiments also exhibited a significant reduction in A beta level in the brain of APP/PS1 mice injected with alpha-syn. These results suggest that alpha-syn aggregated in the brain of AD may act as a protective factor and defend the brain tissue from early A beta deposition and cognitive deficits.