The Mechanisms of the Roles of α-Synuclein, Amyloid-β, and Tau Protein in the Lewy Body Diseases: Pathogenesis, Early Detection, and Therapeutics

Lewy body diseases (LBD) are pathologically defined as the accumulation of Lewy bodies composed of an aggregation of alpha-synuclein (aSyn). In LBD, not only the sole aggregation of alpha Syn but also the co-aggregation of amyloidogenic proteins, such as amyloid-beta (A beta) and tau, has been reported. In this review, the pathophysiology of co-aggregation of aSyn, A beta, and tau protein and the advancement in imaging and fluid biomarkers that can detect aSyn and co-occurring A beta and/or tau pathologies are discussed. Additionally, the alpha Syn-targeted disease-modifying therapies in clinical trials are summarized.

Automated summary

LBD is a disease characterized by the accumulation of Lewy bodies composed of alpha-synuclein (aSyn). This review discusses the co-aggregation of aSyn, amyloid-beta (A beta), and tau proteins, as well as advancements in imaging and fluid biomarkers for detecting these pathologies. It also summarizes the current clinical trials of disease-modifying therapies targeting aSyn.