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Environmental toxicants, including certain pesticides, industrial chemicals, and air pollution are therefore plausible trigger mechanisms for Parkinson\u2019s disease and dementia with Lewy bodies.<\/jats:p>\n                  <jats:p>Here, we propose that toxicants inhaled through the nose can lead to pathological changes in alpha-synuclein in the olfactory system that subsequently spread and give rise to a brain-first subtype of Lewy body disease. Similarly, ingested toxicants can pass through the gut and cause alpha-synuclein pathology that then extends via parasympathetic and sympathetic pathways to ultimately produce a body-first subtype.<\/jats:p>\n                  <jats:p>The resulting spread can be tracked by the development of symptoms, clinical assessments, in vivo imaging, and ultimately pathological examination. The integration of environmental exposures into the brain-first and body-first models generates testable hypotheses, including on the prevalence of the clinical conditions, their future incidence, imaging patterns, and pathological signatures.<\/jats:p>\n                  <jats:p>The proposed link, though, has limitations and leaves many questions unanswered, such as the role of the skin, the influence of the microbiome, and the effects of ongoing exposures. Despite these limitations, the interaction of exogenous factors with the nose and the gut may explain many of the mysteries of Parkinson\u2019s disease and open the door toward the ultimate goal \u2013prevention.<\/jats:p>","DOI":"10.3233\/jpd-240019","type":"journal-article","created":{"date-parts":[[2024,4,9]],"date-time":"2024-04-09T10:35:42Z","timestamp":1712658942000},"page":"363-381","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":39,"title":["The Body, the Brain, the Environment, and Parkinson\u2019s Disease"],"prefix":"10.1177","volume":"14","author":[{"given":"E. 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