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Advanced Neurology Alpha-synuclein, depression and neurodegeneration

uncertainty or error in each parameter that could affect with exposure to environmental toxins. Although these
the certainty of any conclusions drawn from these results. results cannot be taken as definitive, they highlight the need
Second, any conclusions regarding causation should be for further investigations into the molecular mechanisms
considered provisional: evidence of significant cross- underlying this relationship. These results may be of value
sectional or cross-lagged correlations does not necessarily to those examining the shared pathophysiological basis of
imply a causal chain linking genetic variations, depressive these conditions and pave the way for early intervention or
disorders, and neurodegenerative disorders. Third, as the preventive strategies for both PD and AlzD.
estimates used in this study covered countries in whole,
they cannot account for variations within a country, such Acknowledgments
as urban/rural differences in particulate matter pollution None.
or pesticide exposure. Fourth, the number of cases
available for population genetic analysis was relatively low, Funding
and it was based on a relatively small number of volunteers
who were willing to participate in research on allele None.
frequencies. Fifth, the results obtained at the national level Conflict of interest
cannot be extrapolated directly to individuals. Sixth, since
the research focus was on α-synuclein, other genes that The author declares that he has no competing interests.
may be involved in mediating the link between depression,
environmental toxins, and neurodegenerative disorders, Author contributions
such as those involved in dopaminergic transmission or This is a single-authored manuscript.
inflammation, were not analyzed. Finally, the effects of
other environmental factors that may be associated with Ethics approval and consent to participate
both AlzD and PD, such as diet, smoking, and other Not applicable.
occupational exposures, could not be assessed in a study
of this sort due to a lack of large-scale, cross-national data. Consent for publication
It should also be noted that epidemiological findings, Not applicable.
even if replicated, represent a starting point for further
research and not an end in themselves. To translate these Availability of data
findings into improved diagnostic and early intervention All the data used in this study were obtained from public
strategies, a deeper understanding of the molecular domain databases that have been cited in the paper.
links between depression and neurodegeneration as
well as the gene-environment interactions mediating A complete data sheet is available from the author, without
these links is required. Innovative approaches aimed at undue reservation, on request.
elucidating this association include studies of epigenome Further disclosure
or transcriptome [108,109] and genome-wide association
studies that identify shared genetic components across This paper has been uploaded to or deposited in a preprint
these disorders [110] . The associations between the normal server at Preprints (doi: 10.20944/preprints202209.0197.v1).
processes involved in brain aging and those implicated However, the current paper is a substantial revision of the
in neurodegeneration also represent a fruitful line of preprint and contains new results (longitudinal analyses)
inquiry, given that depression may be associated with that were not included in the original preprint.
both these phenomena [111] . Such research would build
on the foundations laid by epidemiological and genetic References
association studies and lead to a precision medicine-based 1. Ou Z, Pan J, Tang S, et al., 2021, Global trends in the
approach to early intervention in PD and AlzD. incidence, prevalence and years lived with disability in
Parkinson’s disease in 204 countries/territories from 1990 to
5. Conclusion 2019. Front Public Health, 9: 776847.

Despite certain inherent methodological limitations, the https://doi.org/10.3389/fpubh.2021.776847
current study provides some evidence of a significant 2. GBD 2019 Dementia Forecasting Collaborators, 2022,
association between depressive disorders, particularly Estimation of the global prevalence of dementia in 2019 and
dysthymia, and the subsequent risk of PD and AlzD. This forecasted prevalence in 2050: An analysis for the Global
relationship may be partly related to the functional variants of Burden of Disease Study 2019. Lancet Public Health, 7:
the α-synuclein gene SNCA, either alone or in combination e105–e125.

Volume 2 Issue 1 (2023) 9 https://doi.org/10.36922/an.326