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

Int J Mol Sci. 2023 Jun 17;24(12):10215. doi: 10.3390/ijms241210215.

Abstract

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

Keywords: Lewy body diseases; Parkinson’s disease; aggregation; amyloid-β; dementia with Lewy bodies; tau protein; α-synuclein.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease* / metabolism
  • Amyloid beta-Peptides / metabolism
  • Humans
  • Lewy Bodies / metabolism
  • Lewy Body Disease* / diagnosis
  • Lewy Body Disease* / metabolism
  • Lewy Body Disease* / therapy
  • alpha-Synuclein / metabolism
  • tau Proteins / metabolism

Substances

  • alpha-Synuclein
  • tau Proteins
  • Amyloid beta-Peptides