19
Apr
Research Links Parkinson’s and Lewy Body Disease with Chemical Effects on Brain and Gut
(Beyond Pesticides, April 19, 2024) Parkinson’s disease (PD) and certain forms of dementia have been associated with exposure to pesticides, industrial chemicals, and air pollution for decades. But the mechanisms of disease progression have been unclear, and U.S. regulators have been reluctant to recognize the risks. Now neurologist E. Ray Dorsey, MD of the University of Rochester and researchers from the University of Alabama at Birmingham and Aarhus University in Denmark propose a new research paradigm based on tracking how toxicants cause neurodegeneration through inhalation and ingestion pathways.
The paradigm, the authors believe, can be used to gain insight into how PD and a form of dementia known as Lewy body disease (LBD) are initiated as many as 50 years before the onset of symptoms. Dorsey and colleagues build on a recent theory that PD and LBD may be two versions of the same basic disease, both involving Lewy bodies in the nervous system.
The group’s proposal was published in the Journal of Parkinson’s Disease in April. If its recommended research agenda produces the anticipated empirical support, the new paradigm will demand integration of many interdisciplinary lines of evidence showing that environmental exposures to synthetic chemicals may be the primary cause of the worldwide epidemic of neurodegenerative disease. Regulatory capture by industry and spineless policy responses to it will no longer suffice to prevent reimagining chemicals policy at a most basic level.
A symposium to discuss the proposed paradigm will occur on Monday, May 20 from 9:00 a.m. to 5:30 p.m. at the Phillips Collection, 1600 21st Street NW, Washington, D.C. Sessions will be moderated by journalists Katie Couric, Jake Tapper, and others. The Michael J. Fox Foundation is a major conference funder.
Dorsey and colleagues review the mounting evidence that PD and LBD have two principal routes to their ultimate neurological harms. One, known as “brain-first,” is quite direct: inhaled through the nose, a toxicant can travel to the olfactory bulb in the brain, from which it spreads to many other brain structures. The second route, through ingestion, called “body-first,” takes the toxicant to the gut, where it initiates the Lewy body disorder in the enteric nervous system (ENS or digestive system’s nervous system). Lewy bodies then propagate into the parasympathetic nervous system, the central nervous system and the brain. Thus, according to this paradigm, the dysfunctions associated with PD and LBD affect the entire neurological network of the body, not just the brain.
The researchers estimate that the majority of LBD cases and about a third of PD cases result from the body-first route. The timing of onset of various symptoms such as loss of motor control, sleep disorders and dementia varies according to the route.
One of the pesticides associated with PD is paraquat, a powerful herbicide currently registered by EPA for application only by licensed operators. Our April 16 Daily News Brief delineates the reasons paraquat should be taken off the market entirely.
Paraquat presents myriad health hazards—EPA itself says, “One small sip can be fatal and there is no antidote.” Beyond this direct lethality to humans and many other organisms, paraquat is linked to thyroid cancer, lung fibrosis, endocrine disruption and liver tumors. It was banned in the European Union in 2007; currently more than 60 countries prohibit its use. But EPA refused to accept the mounting evidence that paraquat is implicated in PD, stating in a 2019 human health risk assessment that for both occupational and non-occupational exposures, there is “insufficient epidemiologic evidence of a clear associative or causal relationship.” This echoes paraquat manufacturer Syngenta’s position in class action litigation brought by PD victims. One bright spot is that the California Assembly is currently considering phasing out paraquat from all uses by the end of 2025.
Only 15 percent of PD victims have a family history of the disease, which implies that environmental factors—and likely multiple simultaneous insults—are involved. Toxicants linked to PD and LBD include not just paraquat but also organochlorine pesticides, trichloroethylene and perchloroethylene (largely responsible, along with benzene and vinyl chloride, for the severe water contamination at Camp Lejeune in California), and particulates from fossil fuel air pollution and wildfires. Dorsey and colleagues’ literature review includes many studies demonstrating PD’s and LBD’s association with environmental toxicants. “In rural areas,” they write, “the prevalence of PD is almost perfectly correlated with pesticide use.” Just drinking well water and working in agriculture are strongly associated with PD prevalence.
The exact processes by which degenerative brain diseases progress remain complex and confusing. PD and LBD resemble Alzheimer’s disease and have some commonality with transmissible spongiform encephalopathies such as Creutzfeldt-Jakob disease, “mad cow,” and the sheep disease scrapie. In PD and LBD, a protein called alpha-synuclein (α-Syn) is important to neuronal signaling. It is something of an oddity, being able to fold itself into multiple configurations even in healthy brains, but is also prone to misfold in ways that interfere with neurotransmitters. During development of PD and LBD, clumps of α-Syn called Lewy bodies form. Once this happens, neurons die and various neurological processes affecting motor coordination, sleep, memory and many other functions begin to fail. Dorsey’s team suggest that α-Syn behaves something like the prions that misfold to induce the transmissible encephalopathies. One misfolded protein can trigger another to copy it, propagating the problem throughout a nervous system.
The authors emphasize that not everyone exposed to environmental toxicants develops PD or LBD. Age at exposure, length of exposure, the involvement of multiple toxicants, and other factors influence the outcome. While a family history of PD and LBD accounts for a small percentage of cases, it does raise the risk of contracting the diseases, and several genes are known to be involved. Little of their influence is understood. At the same time, however, Dorsey and colleagues write that despite having known for a generation about environmental factors, “[We] have fundamentally underinvested in and under-investigated the role environmental toxicants are playing.”
Much research remains to determine the validity of the double-route toxicant paradigm. Clearly there must be research into enteric Lewy bodies and their propagation throughout the whole body nervous system. Dorsey and colleagues suggest approaches for further investigation of exposure scenarios, including comparative analysis of environmental samples such as air, water, and food, as well as biomonitoring samples such as breast milk, urine and blood; and geospatial mapping of PD/LBD prevalence in areas where pesticides and industrial chemicals are present. They also find reason to hope that the severity of these incurable, devastating and fatal diseases can be reduced if exposures are reduced even after disease onset.
Proving the principle will require interdisciplinary studies and synthesis of results from numerous research specialties. If it pans out, it will throw open the gates of inquiry and destabilize chemicals policy, because if PD, LBD and other neurodegenerative diseases are initiated by environmental exposures through the gut and olfactory pathways to the nervous system, the causes of these diseases can no longer be considered in piecemeal fashion. They cannot be entirely explained as mysterious ailments that randomly strike unfortunate people, or are determined by genes. They must be considered as manifestations of the fossil fuel system that is destroying the health of humans and ecosystems and dealt with at the scale of the problem.
For more information on the adverse health impacts of paraquat, see its entries in Beyond Pesticides’ Gateway on Pesticide Hazards and Safe Pest Management and Pesticide-Induced Disease Database.
All unattributed positions and opinions in this piece are those of Beyond Pesticides.
Sources:
The Body, the Brain, the Environment, and Parkinson’s Disease
Dorsey, E. Ray et al.
Journal of Parkinson’s Disease
1 Jan. 2024: 1 – 19.
https://content.iospress.com/articles/journal-of-parkinsons-disease/jpd240019
Risk of Parkinson Disease Among Service Members at Marine Corps Base Camp Lejeune
Samuel M. Goldman et al.
JAMA Neurol. 2023;80(7):673-681. doi:10.1001/jamaneurol.2023.1168
https://jamanetwork.com/journals/jamaneurology/article-abstract/2805037
Brain and Environment Symposium: A day-long symposium to uncover the influence of environmental toxicants on brain disorders
https://brainandenvironment.org/
Comment submitted by Beyond Pesticides
Paraquat Interim Registration Review
March 29, 2024
EPA-HQ-OPP-2011-0855
https://downloads.regulations.gov/EPA-HQ-OPP-2011-0855-0339/attachment_1.pdf
Secret files suggest chemical giant feared weedkiller’s link to Parkinson’s disease
Documents seen by Guardian detail effort to refute scientific research into paraquat and derail nomination of key EPA adviser
by Carey Gillam and Aliya Uteuova
https://www.theguardian.com/us-news/2022/oct/20/syngenta-weedkiller-pesticide-parkinsons-disease-paraquat-documents
