Projections for prevalence of Parkinson’s disease and its driving factors in 195 countries and territories to 2050: modelling study of Global Burden of Disease Study 2021

Dear Editor

The study by Su et al. is particularly significant as it provides a global projection of Parkinson’s disease prevalence through 2050. However, as the researchers acknowledge among the study’s limitations, the modeling could not directly incorporate the effects of environmental and toxicological factors due to the lack of standardized global data.
This omission raises a crucial question: could the rapid rise in Parkinson’s disease not simply be a consequence of aging but also the result of chronic and cumulative exposure to environmental neurotoxins, with a long latency period between initial exposure and clinical manifestation?
Given this perspective, it becomes essential to reconsider the approach to studying Parkinson’s disease, expanding research to include the role of environmental pollution and toxic substances to which individuals are exposed from birth.
If the increase in Parkinson’s cases were solely a matter of aging, we would expect a proportional rise aligned with the growth of the elderly population. However, the growth rate of Parkinson’s cases exceeds demographic projections, suggesting that additional factors are at play. This hypothesis inevitably leads to the question: Is Parkinson’s truly just an age-related disease, or is it the result of cumulative toxic exposures that, over decades, surpass a critical threshold and trigger neurodegeneration?
It is well established that certain substances can selectively damage dopaminergic neurons. Pesticides (1), heavy metals (2), industrial solvents (3), air pollutants (4), and more recently, microplastics and nanoplastics (5) have all been linked to an increased risk of Parkinson’s in various studies. What remains unclear is the role of chronic, low-dose, repeated exposure over time and the possibility that damage accumulates insidiously until it exceeds the nervous system’s compensatory capacity. Further research is needed, as most studies focus on binary or ternary mixtures, whereas it is crucial to investigate more complex mixtures representative of real-world exposure. Does Parkinson’s result from a complex interaction of multiple toxic factors over time (6)? What if the disease is not triggered by a single acute exposure but rather by the slow saturation of the brain with neurotoxic agents that progressively accumulate until a tipping point is reached?
In this context, the role of microplastics, nanoplastics, and their ultrafine components (7) warrants particular attention. Now ubiquitous in the environment and even within the human body, these particles can cross the blood-brain barrier and interact with brain tissue. Moreover, they can act as carriers for other toxic substances, such as pesticides and heavy metals, amplifying their harmful effects. It is not difficult to imagine that, in an individual exposed from birth to these particles and the toxins they carry, the nervous system may experience chronic low-grade inflammation, contributing to neuronal degeneration over time.
The problem is that these environmental risk factors are still considered secondary in large-scale epidemiological analyses. Predictive models, such as the one used in this study, rely primarily on demographic and socioeconomic variables without systematically accounting for toxic exposures.
If we consider Parkinson’s a disease shaped by environmental and industrial factors, we must ask what has changed in recent decades. The population has undoubtedly aged, but at the same time, we have radically altered the quality of air, water, and food. We have introduced thousands of synthetic chemicals, many of which are persistent and bioaccumulative, and we have exposed ourselves to unprecedented pollution levels in human history. Can we truly believe that this has no neurological consequences?
Because if our brains are indeed slowly absorbing the toxins of a polluted world, then treating the disease only once it manifests is no longer sufficient. We must understand how to prevent it before it is too late.

References

1. Paul, K.C., Krolewski, R.C., Lucumi Moreno, E. et al. A pesticide and iPSC dopaminergic neuron screen identifies and classifies Parkinson-relevant pesticides. Nat Commun 14, 2803 (2023). https://doi.org/10.1038/s41467-023-38215-z
2. Pyatha S, Kim H, Lee D, Kim K. Association between Heavy Metal Exposure and Parkinson's Disease: A Review of the Mechanisms Related to Oxidative Stress. Antioxidants (Basel). 2022 Dec 15;11(12):2467. doi: 10.3390/antiox11122467. PMID: 36552676; PMCID: PMC9774122.
3. Dorsey ER, Zafar M, Lettenberger SE, Pawlik ME, Kinel D, Frissen M, Schneider RB, Kieburtz K, Tanner CM, De Miranda BR, Goldman SM, Bloem BR. Trichloroethylene: An Invisible Cause of Parkinson's Disease? J Parkinsons Dis. 2023;13(2):203-218. doi: 10.3233/JPD-225047. PMID: 36938742; PMCID: PMC10041423.
4. Krzyzanowski B, Mullan AF, Turcano P, Camerucci E, Bower JH, Savica R. Air Pollution and Parkinson Disease in a Population-Based Study. JAMA Netw Open.2024;7(9):e2433602. doi:10.1001/jamanetworkopen.2024.33602
5. Zhiyong Liu et al., Anionic nanoplastic contaminants promote Parkinson’s disease–associated α-synuclein aggregation.Sci. Adv.9,eadi8716(2023).DOI:10.1126/sciadv.adi8716
6. Martin O, Scholze M, Ermler S, McPhie J, Bopp SK, Kienzler A, Parissis N, Kortenkamp A. Ten years of research on synergisms and antagonisms in chemical mixtures: A systematic review and quantitative reappraisal of mixture studies. Environ Int. 2021 Jan;146:106206. doi: 10.1016/j.envint.2020.106206. Epub 2020 Oct 26. PMID: 33120228.
7. Ghirga G. Beyond Microplastics: The Ultrafine Fraction of Nanoplastics and Their Health Risks. eLetter. Re. BMJ 2025;388:q2890. Published 14 February 2025. https://www.bmj.com/content/388/bmj.q2890/rr-1