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Brain Inflammation and Alzheimer's-Like Pathology in Individuals Exposed to Severe Air Pollution

Instituto Nacional de Pediatría, Mexico City 14410, Mexico, Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, NC 27599-7525, USA

William Reed

Department of Pediatrics and Center for Environmental Medicine, Asthma and Lung Biology, University of North Carolina, 27599-7310, USA

Robert R. Maronpot

National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA

Carlos Henriquez-Roldán

Departamento de Estadística, Universidad de Valparaíso, Chile

Ricardo Delgado-Chavez

Pathology Department, Instituto Nacional de Cancerología, Mexico City, Mexico

Ana Calderón-Garcidueñas

Hospital de Especialidades No. 25, and Centro de Investigación Biomédica del Noreste CIBIN, IMSS, Monterrey, NL, Mexico

Irma Dragustinovis

Hospital de Especialidades No. 25, IMSS, Monterrey, NL, Mexico

Maricela Franco-Lira

Escuela Médico Militar, Universidad del Ejército y Fuerza Aérea, Mexico City, Mexico

Mariana Aragón-Flores

Departamento de Patología, Hospital Central Militar, Mexico City, Mexico

Anna C. Solt

Facultad de Medicina, NUCE, Universidad Nacional Autónoma de México, Mexico City, Mexico

Michael Altenburg

Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, NC 27599-7525, USA

Ricardo Torres-Jardón

Centro de Ciencias de la Atmósfera, Universidad Nacional Autónoma de México, Mexico City, Mexico

James A. Swenberg

Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, NC 27599-7525, USA, Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, NC 27599-7431, USA, james_swenberg{at}unc.edu

Air pollution is a complex mixture of gases (e.g., ozone), particulate matter, and organic compounds present in outdoor and indoor air. Dogs exposed to severe air pollution exhibit chronic inflammation and acceleration of Alzheimer's-like pathology, suggesting that the brain is adversely affected by pollutants. We investigated whether residency in cities with high levels of air pollution is associated with human brain inflammation. Expression of cyclooxygenase-2 (COX2), an inflammatory mediator, and accumulation of the 42-amino acid form of β-amyloid (Aβ42), a cause of neuronal dysfunction, were measured in autopsy brain tissues of cognitively and neurologically intact lifelong residents of cities having low (n:9) or high (n:10) levels of air pollution. Genomic DNA apurinic/apyrimidinic sites, nuclear factor-B activation and apolipoprotein E genotype were also evaluated. Residents of cities with severe air pollution had significantly higher COX2 expression in frontal cortex and hippocampus and greater neuronal and astrocytic accumulation of Aβ42 compared to residents in low air pollution cities. Increased COX2 expression and Aβ42 accumulation were also observed in the olfactory bulb. These findings suggest that exposure to severe airpollution is associated with brain inflammation and Aβ 42 accumulation, two causes of neuronal dysfunction that precede the appearance of neuritic plaques and neurofibrillary tangles, hallmarks of Alzheimer's disease.

Key Words: Brain • β-amyloid • cyclooxygenase 2 • inflammation • neuropathology • air pollution • Mexico City.

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Toxicologic Pathology, Vol. 32, No. 6, 650-658 (2004)
DOI: 10.1080/01926230490520232


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This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Calderón-Garcidueñas, L. Articles by Swenberg, J. A. Search for Related Content PubMed PubMed Citation Articles by Calderón-Garcidueñas, L. Articles by Swenberg, J. A. Pubmed/NCBI databases Substance via MeSH Medline Plus Health Information Air Pollution Alzheimer's Disease Encephalitis Social Bookmarking                         What's this?