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Advanced Neurology

ORIGINAL RESEARCH ARTICLE
Alpha-synuclein at the interface between

depression and neurodegeneration: Evidence
from epidemiological and genetic data

Ravi Philip Rajkumar*

Department of Psychiatry, Jawaharlal Institute of Postgraduate Medical Education and Research,
Pondicherry, India

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
*Corresponding author:
Ravi Philip Rajkumar matter pollution. The significance of these results is discussed in light of existing
(ravi.psych@gmail.com) translational, clinical, and epidemiological research on the links between these
disorders.
Citation: Rajkumar RP, 2023,
Alpha-synuclein at the interface
between depression and
neurodegeneration: Evidence from Keywords: Alpha-synuclein; SNCA; Major depression; Dysthymia; Parkinson’s disease;
epidemiological and genetic data. Epidemiology
Adv Neuro, 2(1): 326.
https://doi.org/10.36922/an.326
Received: January 16, 2023
Accepted: February 21, 2023 1. Introduction
Published Online: March 6, 2023 Alzheimer’s disease (AlzD) and Parkinson’s disease (PD) are the most prevalent
neurodegenerative disorders globally [1,2] . The burden associated with these disorders
Copyright: © 2023 Author(s).
This is an Open-Access article is expected to increase substantially over the next three decades, particularly in
distributed under the terms of the low- and middle-income countries, largely due to demographic shifts [3,4] . Both these
Creative Commons Attribution disorders are chronic and progressive in nature, and they are associated with substantial
License, permitting distribution,
and reproduction in any medium, disability, caregiver burden, and financial loss [5-8] . AlzD is mainly characterized by
provided the original work is progressive memory impairment and loss of other cognitive functions , while PD is
[9]
properly cited. characterized by progressive motor symptoms and disability . Despite their clinical and
[10]
Publisher’s Note: AccScience pathophysiological distinctiveness, there are significant clinical and neuropathological
Publishing remains neutral with overlaps between them. Clinically, PD is associated with high rates of cognitive
regard to jurisdictional claims in [11]
published maps and institutional impairment, including dementia ; likewise, a subset of patients with AlzD tend to show
[12]
affiliations. signs of parkinsonism . Pathologically, beta-amyloid (β-amyloid) deposition, which
Volume 2 Issue 1 (2023) 1 https://doi.org/10.36922/an.326