摘要

Parkinson's disease (PD) is an age-related neurodegenerative disorder characterized by dopaminergic neural cell death in the substantia nigra of the brain and alpha-synuclein (alpha-syn) accumulation in Lewy bodies. alpha-Syn can be detected in blood and is a potential biomarker for PD. It has been shown recently that alpha-syn can pass through the blood-brain barrier (BBB), but the mechanism is not yet understood. We hypothesized that alpha-syn could interact with lipoproteins, and in association with these particles, could pass through the BBB. Here, we show that apoE, apoJ, and apoA1, but not apoB, were co-immunocaptured along with alpha-syn from human blood plasma, suggesting that alpha-syn is associated with high-density lipoproteins (HDL). This association was also supported by experiments involving western blotting of plasma fractions separated by gel filtration, which revealed that alpha-syn was found in fractions identified as HDL. Interestingly, we could also detect alpha-syn and ApoJ in the intermediate fraction between HDL and LDL, referred to as lipoprotein (a) (Lp(a)), which has an important role in cholesterol metabolism. Overall, the results provide best support for the hypothesis that alpha-syn interacts with HDL, and this has potential implications for transport of alpha-syn from the brain to peripheral blood, across the BBB.

  • 出版日期2017-10