Long-term Air Pollution Exposure Is Associated with Neuroinflammation, an Altered Innate Immune Response, Disruption of the Blood-Brain Barrier, Ultrafine Particulate Deposition, and Accumulation of Amyloid β-42 and α-Synuclein in Children and Young Adults
Abstract
Air pollution is a serious environmental problem. We investigated whether residency in cities with high air pollution is associated with neuroinflammation/neurodegeneration in healthy children and young adults who died suddenly. We measured mRNA cyclooxygenase-2, interleukin-1beta, and CD14 in target brain regions from low (n = 12) or highly exposed residents (n = 35) aged 25.1 +/- 1.5 years. Upregulation of cyclooxygenase-2, interleukin-1beta, and CD14 in olfactory bulb, frontal cortex, substantia nigrae and vagus nerves; disruption of the blood-brain barrier; endothelial activation, oxidative stress, and inflammatory cell trafficking were seen in highly exposed subjects. Amyloid beta42 (Abeta42) immunoreactivity was observed in 58.8% of apolipoprotein E (APOE) 3/3 < 25 y, and 100% of the APOE 4 subjects, whereas alpha-synuclein was seen in 23.5% of < 25 y subjects. Particulate material (PM) was seen in olfactory bulb neurons, and PM < 100 nm were observed in intraluminal erythrocytes from lung, frontal, and trigeminal ganglia capillaries. Exposure to air pollution causes neuroinflammation, an altered brain innate immune response, and accumulation of Abeta42 and alpha-synuclein starting in childhood. Exposure to air pollution should be considered a risk factor for Alzheimer's and Parkinson's diseases, and carriers of the APOE 4 allele could have a higher risk of developing Alzheimer's disease if they reside in a polluted environment.
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Studies of individual components of air pollution have found links to neurodevelopmental outcomes, including effects on IQ, language development, executive function, and psychomotor development.
“Studies of individual components of air pollution have found links to neurodevelopmental outcomes, including effects on intelligence quotient (IQ), language development, executive function, and psychomotor development [7–10].”
From A Systematic Review and Meta-Analysis of Multiple Airborne Pollutants and Autism Spectrum Disorder (2016) · cites this paper as [7]
Cites
Griffin, W. S. T., & Mrak, R. E. (2002) · Journal of Leukocyte Biology · doi:10.1189/jlb.72.2.233 · Cited by 248 · see citing works
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Air Pollution and Cardiovascular Disease
Rajagopalan, S., Al-Kindi, S. G., & Brook, R. D. (2018) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2018.07.099 · Cited by 1,299 · see citing works
Chen, H., Kwong, J. C., Copes, R., Tu, K., Villeneuve, P. J., van Donkelaar, A., Hystad, P., Martin, R. V., Murray, B. J., Jessiman, B., et al. (2017) · The Lancet · doi:10.1016/s0140-6736(16)32399-6 · Cited by 776 · see citing works
Air Pollution and Dementia: A Systematic Review
Peters, R., Ee, N., Peters, J., Booth, A., Mudway, I., & Anstey, K. J. (2019) · Journal of Alzheimer’s Disease · doi:10.3233/jad-180631 · Cited by 548 · see citing works
The outdoor air pollution and brain health workshop
Block, M. L., Elder, A., Auten, R. L., Bilbo, S. D., Chen, H., Chen, J.-C., Cory-Slechta, D. A., Costa, D., Diaz-Sanchez, D., Dorman, D. C., et al. (2012) · NeuroToxicology · doi:10.1016/j.neuro.2012.08.014 · Cited by 539 · see citing works
Power, M. C., Adar, S. D., Yanosky, J. D., & Weuve, J. (2016) · NeuroToxicology · doi:10.1016/j.neuro.2016.06.004 · Cited by 422 · see citing works
Long-term exposure to traffic-related particulate matter impairs cognitive function in the elderly
Ranft, U., Schikowski, T., Sugiri, D., Krutmann, J., & Krämer, U. (2009) · Environmental Research · doi:10.1016/j.envres.2009.08.003 · Cited by 410 · see citing works
Exposure to ambient air pollution and the incidence of dementia: a population-based cohort study
Chen, H., Kwong, J. C., Copes, R., Hystad, P., van Donkelaar, A., Tu, K., Brook, J. R., Goldberg, M. S., Martin, R. V., Murray, B. J., et al. (2017) · Environment International · doi:10.1016/j.envint.2017.08.020 · Cited by 394 · see citing works
Jung, C.-R., Lin, Y.-T., & Hwang, B.-F. (2015) · Journal of Alzheimer's Disease · doi:10.3233/jad-140855 · Cited by 380 · see citing works
Levesque, S., Taetzsch, T., Lull, M. E., Kodavanti, U., Stadler, K., Wagner, A., Johnson, J. A., Duke, L., Kodavanti, P., Surace, M. J., et al. (2011) · Environmental Health Perspectives · doi:10.1289/ehp.1002986 · Cited by 371 · see citing works
Herbert, M. R. (2010) · Current Opinion in Neurology · doi:10.1097/wco.0b013e328336a01f · Cited by 356 · see citing works
Calderón-Garcidueñas, L., Engle, R., Mora-Tiscareño, A., Styner, M., Gómez-Garza, G., Zhu, H., Jewells, V., Torres-Jardón, R., Romero, L., Monroy-Acosta, M. E., et al. (2011) · Brain and Cognition · doi:10.1016/j.bandc.2011.09.006 · Cited by 323 · see citing works
Self-citationAre noise and air pollution related to the incidence of dementia? A cohort study in London, England
Carey, I. M., Anderson, H. R., Atkinson, R. W., Beevers, S. D., Cook, D. G., Strachan, D. P., Dajnak, D., Gulliver, J., & Kelly, F. J. (2018) · BMJ Open · doi:10.1136/bmjopen-2018-022404 · Cited by 302 · see citing works
Grande, G., Ljungman, P. L. S., Eneroth, K., Bellander, T., & Rizzuto, D. (2020) · JAMA Neurology · doi:10.1001/jamaneurol.2019.4914 · Cited by 282 · see citing works
Air Pollution, Oxidative Stress, and Alzheimer's Disease
Moulton, P. V., & Yang, W. (2012) · Journal of Environmental and Public Health · doi:10.1155/2012/472751 · Cited by 265 · see citing works
Han, Y., Wang, B., Gao, H., He, C., Hua, R., Liang, C., Zhang, S., Wang, Y., Xin, S., & Xu, J. (2022) · Journal of Inflammation Research · doi:10.2147/jir.s384949 · Cited by 265 · see citing works
A Systematic Review and Meta-Analysis of Multiple Airborne Pollutants and Autism Spectrum Disorder
Lam, J., Sutton, P., Kalkbrenner, A., Windham, G., Halladay, A., Koustas, E., Lawler, C., Davidson, L., Daniels, N., Newschaffer, C., et al. (2016) · PLOS ONE · doi:10.1371/journal.pone.0161851 · Cited by 247 · see citing works
Shi, L., Steenland, K., Li, H., Liu, P., Zhang, Y., Lyles, R. H., Requia, W. J., Ilango, S. D., Chang, H. H., Wingo, T., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-27049-2 · Cited by 239 · see citing works
Gene–environment interactions in Alzheimer disease: the emerging role of epigenetics
Migliore, L., & Coppedè, F. (2022) · Nature Reviews Neurology · doi:10.1038/s41582-022-00714-w · Cited by 217 · see citing works
Singh, N., Singh, S., & Mall, R. K. (2020) · Urban Ecology · doi:10.1016/b978-0-12-820730-7.00017-3 · Cited by 211 · see citing works
Association of traffic-related air pollution with cognitive development in children
Freire, C., Ramos, R., Puertas, R., Lopez-Espinosa, M.-J., Julvez, J., Aguilera, I., Cruz, F., Fernandez, M.-F., Sunyer, J., & Olea, N. (2010) · Journal of Epidemiology and Community Health · doi:10.1136/jech.2008.084574 · Cited by 183 · see citing works
Gerlofs-Nijland, M. E., van Berlo, D., Cassee, F. R., Schins, R. P., Wang, K., & Campbell, A. (2010) · Particle and Fibre Toxicology · doi:10.1186/1743-8977-7-12 · Cited by 170 · see citing works
Newman, N. C., Ryan, P., LeMasters, G., Levin, L., Bernstein, D., Hershey, G. K. K., Lockey, J. E., Villareal, M., Reponen, T., Grinshpun, S., et al. (2013) · Environmental Health Perspectives · doi:10.1289/ehp.1205555 · Cited by 160 · see citing works
Adami, G., Pontalti, M., Cattani, G., Rossini, M., Viapiana, O., Orsolini, G., Benini, C., Bertoldo, E., Fracassi, E., Gatti, D., et al. (2022) · RMD Open · doi:10.1136/rmdopen-2021-002055 · Cited by 148 · see citing works
Association between Early Life Exposure to Air Pollution and Working Memory and Attention
Rivas, I., Basagaña, X., Cirach, M., López-Vicente, M., Suades-González, E., Garcia-Esteban, R., Álvarez-Pedrerol, M., Dadvand, P., & Sunyer, J. (2019) · Environmental Health Perspectives · doi:10.1289/ehp3169 · Cited by 140 · see citing works
Oudin, A., Segersson, D., Adolfsson, R., & Forsberg, B. (2018) · PLOS ONE · doi:10.1371/journal.pone.0198283 · Cited by 133 · see citing works
Woodward, N. C., Haghani, A., Johnson, R. G., Hsu, T. M., Saffari, A., Sioutas, C., Kanoski, S. E., Finch, C. E., & Morgan, T. E. (2018) · Translational Psychiatry · doi:10.1038/s41398-018-0317-1 · Cited by 118 · see citing works
Calderón-Garcidueñas, L., González-Maciel, A., Reynoso-Robles, R., Kulesza, R. J., Mukherjee, P. S., Torres-Jardón, R., Rönkkö, T., & Doty, R. L. (2018) · Environmental Research · doi:10.1016/j.envres.2018.06.027 · Cited by 110 · see citing works
Self-citationLower test scores from wildfire smoke exposure
Wen, J., & Burke, M. (2022) · Nature Sustainability · doi:10.1038/s41893-022-00956-y · Cited by 104 · see citing works
Loop, M. S., Kent, S. T., Al-Hamdan, M. Z., Crosson, W. L., Estes, S. M., Estes, M. G., Quattrochi, D. A., Hemmings, S. N., Wadley, V. G., & McClure, L. A. (2013) · PLoS ONE · doi:10.1371/journal.pone.0075001 · Cited by 99 · see citing works
Kirrane, E. F., Bowman, C., Davis, J. A., Hoppin, J. A., Blair, A., Chen, H., Patel, M. M., Sandler, D. P., Tanner, C. M., Vinikoor-Imler, L., et al. (2015) · Journal of Occupational & Environmental Medicine · doi:10.1097/jom.0000000000000451 · Cited by 100 · see citing works
Levesque, S., Taetzsch, T., Lull, M. E., Johnson, J. A., McGraw, C., & Block, M. L. (2013) · Journal of Neurochemistry · doi:10.1111/jnc.12231 · Cited by 94 · see citing works
Air Pollution and Incidence of Dementia: A Systematic Review and Meta-analysis
Abolhasani, E., Hachinski, V., Ghazaleh, N., Azarpazhooh, M. R., Mokhber, N., & Martin, J. (2023) · Neurology · doi:10.1212/wnl.0000000000201419 · Cited by 88 · see citing works
Croze, M. L., & Zimmer, L. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-170857 · Cited by 78 · see citing works
Is air pollution associated with increased risk of cognitive decline? A systematic review
Peters, R., Peters, J., Booth, A., & Mudway, I. (2015) · Age and Ageing · doi:10.1093/ageing/afv087 · Cited by 65 · see citing works
Jeong, S., Park, S. A., Park, I., Kim, P., Cho, N. H., Hyun, J. W., & Hyun, Y.-M. (2019) · Journal of Immunology Research · doi:10.1155/2019/3486841 · Cited by 64 · see citing works
Daulatzai, M. A. (2015) · Journal of Neural Transmission · doi:10.1007/s00702-015-1404-6 · Cited by 63 · see citing works
He, F., Tang, J., Zhang, T., Lin, J., Li, F., Gu, X., Chen, A., Nevill, A., & Chen, R. (2022) · Environmental Research · doi:10.1016/j.envres.2021.112318 · Cited by 34 · see citing works
The Role of Genetic, Environmental, and Dietary Factors in Alzheimer’s Disease: A Narrative Review
Mertaş, B., & Boşgelmez, İ. İ. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26031222 · Cited by 35 · see citing works
- Authors
- Calderón-Garcidueñas, L., Solt, A. C., Henríquez-Roldán, C., Torres-Jardón, R., Nuse, B., Herritt, L., Villarreal-Calderón, R., Osnaya, N., Stone, I., García, R., Brooks, D. M., González-Maciel, A., Reynoso-Robles, R., Delgado-Chávez, R., & Reed, W.
- Affiliations
- Instituto Nacional de Pediatría, Mexico City, Mexico
- Harvard University (US)
- University of Valparaíso (CL)
- Centro de Ciencias de la Atmósfera, Universidad Nacional Autónoma de México, Mexico City, Mexico
- University of Montana (US)
- Davidson Honors College, The University of Montana, Missoula, Montana, USA
- Instituto Nacional de Pediatria (MX)
- Pathology Department, Instituto Nacional de Cancerología, Mexico City, Mexico
- University of North Carolina at Chapel Hill (US)
- Venue
- Toxicologic Pathology
- Publisher
- SAGE Publications
- Published
- 2008-02
- Volume
- 36
- Issue
- 2
- Pages
- 289-310
- ISSN
- 0192-6233 (ISSN-L)
- 1533-1601
- OpenAlex
- W2128903550
- Cited by
- 937
- References
- 1
- Citations by year
- 2026: 58 · 2025: 72 · 2024: 83 · 2023: 67 · 2022: 70 · 2021: 95 · 2020: 90 · 2019: 62 · 2018: 61 · 2017: 45 · 2016: 48 · 2015: 50 · 2014: 25 · 2013: 29 · 2012: 22
- FWCI
- 13.77
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Toxicologic Pathology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (K01NS046410, 1KO1 NS046410-01A1)
- National Institute of Environmental Health Sciences (R21ES013293)
- National Center for Research Resources (P20RR015583)
- Topics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Air Quality and Health Impacts
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Indoor Air Quality and Microbial Exposure
- Keywords
- air pollution, neuroinflammation, innate immune response, blood-brain barrier disruption, ultrafine particles, amyloid-beta 42, alpha-synuclein, APOE ε4, cyclooxygenase-2, IL-1β, CD14, olfactory bulb, substantia nigra, vagus nerve, sudden death, children and young adults, Alzheimer's disease risk, Parkinson's disease risk, endothelial activation, oxidative stress
- MeSH terms
- Adolescent, Adult, Air Pollutants, Blood-Brain Barrier, Brain, Child, Child, Preschool, Encephalitis, Female, Humans, Male, Neurons, Olfactory Bulb, Peptide Fragments, RNA, Messenger, Urban Health, Vagus Nerve, Up-Regulation, Amyloid beta-Peptides, Lipopolysaccharide Receptors, Cyclooxygenase 2, alpha-Synuclein, Particulate Matter, Interleukin-1beta
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