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© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Environmental exposures to fine particulate matter (PM2.5) and ultrafine particle matter (UFPM) are associated with overlapping Alzheimer’s, Parkinson’s 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 ± 4.7 y exposed to PM2.5 levels above the USEPA annual standard and to high UFPM and 26 low pollution controls (11.5 ± 4.4 y); 43 MMC adults (42.3 ± 15.9 y) and 14 low pollution adult controls (33.1 ± 12.0 y); and 19 amyotrophic lateral sclerosis (ALS) patients (52.4 ± 14.1 y). TDP-43 neuropathology and cisternal CSF data from 20 subjects—15 MMC (41.1 ± 18.9 y) and 5 low pollution controls (46 ± 16.01 y)—were included. CSF TDP-43 exponentially increased with age (p < 0.0001) and it was higher for MMC residents. TDP-43 cisternal CSF levels of 572 ± 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.

Details

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’s Hallmarks. Brain TDP-43 Pathology in MMC Residents Is Associated with High Cisternal CSF TDP-43 Concentrations
Author
Calderón-Garcidueñas, Lilian 1   VIAFID ORCID Logo  ; Stommel, Elijah W 2 ; Lachmann, Ingolf 3   VIAFID ORCID Logo  ; Waniek, Katharina 3 ; Chih-Kai Chao 4   VIAFID ORCID Logo  ; González-Maciel, Angélica 5   VIAFID ORCID Logo  ; García-Rojas, Edgar 6 ; Torres-Jardón, Ricardo 7   VIAFID ORCID Logo  ; Delgado-Chávez, Ricardo 8 ; Mukherjee, Partha S 9   VIAFID ORCID Logo 

 College of Health, The University of Montana, Missoula, MT 59812, USA; Universidad del Valle de México, Mexico City 14370, Mexico 
 Department of Neurology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA 
 Roboscreen GmbH, 04129 Leipzig, Germany 
 College of Health, The University of Montana, Missoula, MT 59812, USA 
 Instituto Nacional de Pediatría, Mexico City 04530, Mexico 
 Universidad del Valle de México, Mexico City 14370, Mexico 
 Instituto de Ciencias de la Atmósfera y Cambio Climático, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico 
 Independent Researcher, Mexico City 04310, Mexico 
 Interdisciplinary Statistical Research Unit, Indian Statistical Institute, Kolkata 700108, India 
First page
559
Publication year
2022
Publication date
2022
Publisher
MDPI AG
e-ISSN
23056304
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2728532923
Copyright
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.