Alpha-synuclein: a pathological factor with A beta and tau and biomarker in Alzheimer's disease

Background: Alpha-synuclein (alpha-syn) is considered the main pathophysiological protein component of Lewy bodies in synucleinopathies. alpha-Syn is an intrinsically disordered protein (IDP), and several types of structural conformations have been reported, depending on environmental factors. Since IDPs may have distinctive functions depending on their structures, alpha-syn can play different roles and interact with several proteins, including amyloid-beta (A beta) and tau, in Alzheimer's disease (AD) and other neurodegenerative disorders. Main body: In previous studies, alpha-syn aggregates in AD brains suggested a close relationship between AD and alpha-syn. In addition, alpha-syn directly interacts with A beta and tau, promoting mutual aggregation and exacerbating the cognitive decline. The interaction of alpha-syn with A beta and tau presented different consequences depending on the structural forms of the proteins. In AD, alpha-syn and tau levels in CSF were both elevated and revealed a high positive correlation. Especially, the CSF alpha-syn concentration was significantly elevated in the early stages of AD. Therefore, it could be a diagnostic marker of AD and help distinguish AD from other neurodegenerative disorders by incorporating other biomarkers. Conclusion: The overall physiological and pathophysiological functions, structures, and genetics of alpha-syn in AD are reviewed and summarized. The numerous associations of alpha-syn with A beta and tau suggested the significance of alpha-syn, as a partner of the pathophysiological roles in AD. Understanding the involvements of alpha-syn in the pathology of A beta and tau could help address the unresolved issues of AD. In particular, the current status of the CSF alpha-syn in AD recommends it as an additional biomarker in the panel for AD diagnosis.