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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 -Synuclein in Children and Young Adults

¹ Instituto Nacional de Pediatría, Mexico City, Mexico
² The College of Health Professions and Biomedical Sciences, The University of Montana, Missoula, Montana, USA
³ South Shore Psychiatric Program, Harvard University, Brockton, Massachusetts, USA
⁴ Departamento de Estadística, Universidad de Valparaíso, Chile
⁵ Centro de Ciencias de la Atmósfera, Universidad Nacional Autónoma de México, Mexico City, Mexico
⁶ Davidson Honors College, The University of Montana, Missoula, Montana, USA
⁷ Pathology Department, Instituto Nacional de Cancerología, Mexico City, Mexico
⁸ Center for Environmental Medicine, Asthma and Lung Biology, and Department of Pediatrics, University of North Carolina, Chapel Hill, North Carolina, USA

Correspondence: Address correspondence to: Lilian Calderón-Garcidueñas, MD, PhD, The Center for Structural and Functional Neurosciences, College of Health Professions and Biomedical Sciences, University of Montana, 32 Campus Drive, 289 Skaggs Bldg., Missoula, MT 59812; e-mail: lilian.calderon-garciduenas{at}umontana.edu.

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-1β, 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-1β, 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 β42 (Aβ42) immunoreactivity was observed in 58.8% of apolipoprotein E (APOE) 3/3 < 25 y, and 100% of the APOE 4 subjects, whereas -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 Aβ42 and -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.

Key Words: -synuclein • Alzheimer’s disease • air pollution • amyloid β42 • neuroinflammation • Parkinson’s disease • ultrafine particulate matter

Abbreviations: Aβ42, beta amyloid • AD, Alzheimer’s disease • APO, E apolipoprotein E • APP, amyloid precursor protein • BBB, blood-brain barrier • COX2, cyclooxygenase 2 • GFAP, glial fibrillary acidic protein • HLA-DR, human leukocyte antigen-DR • IL-1β, interleukin-1β • ICAM-1, intercellular adhesion molecule-1 • IHC, immunohistochemistry • LPS, lipopolysaccharide • MC, Mexico City • MTBE, methyl-ter-butyl ether • NFB, transcription factor nuclear factor kappa-B • NSE, neuron specific enolase • O₃, ozone • OB, olfactory bulb • PD, Parkinson’s disease • PM, particulate matter • PNS, peripheral nervous system • PT, prothrombin • RBC, red blood cells • SNC, substantia nigrae pars compacta • TLR, toll-like receptor • UFPM, ultrafine PM • VCAM-1, vascular adhesion molecule-1 • ZO-1, zonula occludens-1

This version was published on February 1, 2008

Toxicologic Pathology, Vol. 36, No. 2, 289-310 (2008)
DOI: 10.1177/0192623307313011


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