Alpha-synuclein at the interface between depression and neurodegeneration: Evidence from epidemiological and genetic data

Abstract

Parkinson’s disease (PD) and Alzheimer’s disease (AlzD) are the two most common neurodegenerative disorders. Although these two disorders differ in terms of their underlying pathophysiology, clinical features, and course, there is a certain degree of overlap between them. This overlap may be partly related to alpha-synuclein (α-synuclein)-mediated neuropathological changes. Recent evidence has found that depression is associated with increased subsequent risk of both these neurological disorders and α-synuclein may also play a pathogenic role in depression. In the current study, epidemiological, population genetic, and environmental exposure data were examined in relation to the estimated prevalence of depressive disorders, PD, and AlzD using a cross-sectional, country-level analysis. The results showed a significant relationship between depressive disorders and neurodegenerative disorders, a possible shared genetic vulnerability related to the functional polymorphisms of SNCA gene, and potential gene-environment interactions involving fine particulate matter pollution. The significance of these results is discussed in light of existing translational, clinical, and epidemiological research on the links between these disorders.