{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:41:54Z","timestamp":1791232914793,"version":"4.1.0"},"reference-count":130,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,9,24]],"date-time":"2022-09-24T00:00:00Z","timestamp":1663977600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>Environmental exposures to fine particulate matter (PM2.5) and ultrafine particle matter (UFPM) are associated with overlapping Alzheimer\u2019s, Parkinson\u2019s and TAR DNA-binding protein 43 (TDP-43) hallmark protein pathologies in young Metropolitan Mexico City (MMC) urbanites. We measured CSF concentrations of TDP-43 in 194 urban residents, including 92 MMC children aged 10.2 \u00b1 4.7 y exposed to PM2.5 levels above the USEPA annual standard and to high UFPM and 26 low pollution controls (11.5 \u00b1 4.4 y); 43 MMC adults (42.3 \u00b1 15.9 y) and 14 low pollution adult controls (33.1 \u00b1 12.0 y); and 19 amyotrophic lateral sclerosis (ALS) patients (52.4 \u00b1 14.1 y). TDP-43 neuropathology and cisternal CSF data from 20 subjects\u201415 MMC (41.1 \u00b1 18.9 y) and 5 low pollution controls (46 \u00b1 16.01 y)\u2014were included. CSF TDP-43 exponentially increased with age (p &lt; 0.0001) and it was higher for MMC residents. TDP-43 cisternal CSF levels of 572 \u00b1 208 pg\/mL in 6\/15 MMC autopsy cases forecasted TDP-43 in the olfactory bulb, medulla and pons, reticular formation and motor nuclei neurons. A 16 y old with TDP-43 cisternal levels of 1030 pg\/mL exhibited TDP-43 pathology and all 15 MMC autopsy cases exhibited AD and PD hallmarks. Overlapping TDP-43, AD and PD pathologies start in childhood in urbanites with high exposures to PM2.5 and UFPM. Early, sustained exposures to PM air pollution represent a high risk for developing brains and MMC UFPM emissions sources ought to be clearly identified, regulated, monitored and controlled. Prevention of deadly neurologic diseases associated with air pollution ought to be a public health priority and preventive medicine is key.<\/jats:p>","DOI":"10.3390\/toxics10100559","type":"journal-article","created":{"date-parts":[[2022,9,29]],"date-time":"2022-09-29T01:23:16Z","timestamp":1664414596000},"page":"559","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["TDP-43 CSF Concentrations Increase Exponentially with Age in Metropolitan Mexico City Young Urbanites Highly Exposed to PM2.5 and Ultrafine Particles and Historically Showing Alzheimer and Parkinson\u2019s Hallmarks. Brain TDP-43 Pathology in MMC Residents Is Associated with High Cisternal CSF TDP-43 Concentrations"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3130-7895","authenticated-orcid":false,"given":"Lilian","family":"Calder\u00f3n-Garcidue\u00f1as","sequence":"first","affiliation":[{"name":"College of Health, The University of Montana, Missoula, MT 59812, USA"},{"name":"Universidad del Valle de M\u00e9xico, Mexico City 14370, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elijah W.","family":"Stommel","sequence":"additional","affiliation":[{"name":"Department of Neurology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9225-1493","authenticated-orcid":false,"given":"Ingolf","family":"Lachmann","sequence":"additional","affiliation":[{"name":"Roboscreen GmbH, 04129 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Waniek","sequence":"additional","affiliation":[{"name":"Roboscreen GmbH, 04129 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7984-2849","authenticated-orcid":false,"given":"Chih-Kai","family":"Chao","sequence":"additional","affiliation":[{"name":"College of Health, The University of Montana, Missoula, MT 59812, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1909-9146","authenticated-orcid":false,"given":"Ang\u00e9lica","family":"Gonz\u00e1lez-Maciel","sequence":"additional","affiliation":[{"name":"Instituto Nacional de Pediatr\u00eda, Mexico City 04530, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edgar","family":"Garc\u00eda-Rojas","sequence":"additional","affiliation":[{"name":"Universidad del Valle de M\u00e9xico, Mexico City 14370, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1874-6057","authenticated-orcid":false,"given":"Ricardo","family":"Torres-Jard\u00f3n","sequence":"additional","affiliation":[{"name":"Instituto de Ciencias de la Atm\u00f3sfera y Cambio Clim\u00e1tico, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Mexico City 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Delgado-Ch\u00e1vez","sequence":"additional","affiliation":[{"name":"Independent Researcher, Mexico City 04310, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1655-3534","authenticated-orcid":false,"given":"Partha S.","family":"Mukherjee","sequence":"additional","affiliation":[{"name":"Interdisciplinary Statistical Research Unit, Indian Statistical Institute, Kolkata 700108, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.envres.2018.03.023","article-title":"Hallmarks of Alzheimer disease are evolving relentlessly in Metropolitan Mexico City infants, children and young adults. 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