Air Pollution and Children: Neural and Tight Junction Antibodies and Combustion Metals, the Role of Barrier Breakdown and Brain Immunity in Neurodegeneration

Article type: Research Article

Authors: Calderón-Garcidueñas, Lilian^{a; *} | Vojdani, Aristo^b | Blaurock-Busch, Eleonore^c | Busch, Yvette^c | Friedle, Albrecht^c | Franco-Lira, Maricela^d | Sarathi-Mukherjee, Partha^e | Martínez-Aguirre, Xavier^f | Park, Su-Bin^g | Torres-Jardón, Ricardo^h | D'Angiulli, Amedeo^g

Affiliations: [a] The Center for Structural and Functional Neurosciences, The University of Montana, Missoula, MT, USA | [b] Immunosciences Laboratory, Los Angeles, CA, USA | [c] Clinical and Environmental Laboratories, Micro Trace Minerals (MTM), Hersbruck, Germany/Trace Minerals International (TMI), Boulder, CO, USA | [d] Hospital Central Militar, Secretaria de la Defensa Nacional, Mexico City, Mexico | [e] Mathematics Department, Boise State University, Boise, Idaho, USA | [f] Universidad Autónoma de Piedras Negras, UAPN, Piedras Negras, Coahuila, México | [g] NICER Lab, Department of Neuroscience, Carleton University, Ottawa, Ontario, Canada | [h] Centro de Ciencias de la Atmósfera, Universidad Nacional Autónoma de México, Mexico City, Mexico

Correspondence: [*] Correspondence to: Lilian Calderón-Garcidueñas MA, MD, PhD, The Center for Structural and Functional Neurosciences, The University of Montana, 32 Campus Drive, Skaggs Building 287, Missoula, MT 59812, USA. Tel.: +1 406 243 4785; E-mail: lilian.calderon-garciduenas@umontana.edu.

Abstract: Millions of children are exposed to concentrations of air pollutants, including fine particulate matter (PM2.5), above safety standards. In the Mexico City Metropolitan Area (MCMA) megacity, children show an early brain imbalance in oxidative stress, inflammation, innate and adaptive immune response-associated genes, and blood-brain barrier breakdown. We investigated serum and cerebrospinal fluid (CSF) antibodies to neural and tight junction proteins and environmental pollutants in 139 children ages 11.91 ± 4.2 y with high versus low air pollution exposures. We also measured metals in serum and CSF. MCMA children showed significantly higher serum actin IgG, occludin/zonulin 1 IgA, IgG, myelin oligodendrocyte glycoprotein IgG and IgM (p < 0.01), myelin basic protein IgA and IgG, S-100 IgG and IgM, and cerebellar IgG (p < 0.001). Serum IgG antibodies to formaldehyde, benzene, and bisphenol A, and concentrations of Ni and Cd were significantly higher in exposed children (p < 0.001). CSF MBP antibodies and nickel concentrations were higher in MCMA children (p = 0.03). Air pollution exposure damages epithelial and endothelial barriers and is a robust trigger of tight junction and neural antibodies. Cryptic ‘self’ tight junction antigens can trigger an autoimmune response potentially contributing to the neuroinflammatory and Alzheimer and Parkinson's pathology hallmarks present in megacity children. The major factor determining the impact of neural antibodies is the integrity of the blood-brain barrier. Defining the air pollution linkage of the brain/immune system interactions and damage to physical and immunological barriers with short and long term neural detrimental effects to children's brains ought to be of pressing importance for public health.

Keywords: Air pollution, Alzheimer's disease, children, innate and adaptive immunity, neurodegeneration, neuroinflammation, particulate matter, tight junction and neural reactive autoantibodies

DOI: 10.3233/JAD-141365

Journal: Journal of Alzheimer's Disease, vol. 43, no. 3, pp. 1039-1058, 2015