title: Prefrontal white matter pathology in air pollution exposed Mexico City young urbanites and their potential impact on neurovascular unit dysfunction and the development of Alzheimer's disease.
abstract: Millions of urban children are chronically exposed to high concentrations of air pollutants, i.e., fine particulate matter (PM2.5) and ozone, associated with increased risk for Alzheimer's disease. Compared with children living with clear air those in Mexico City (MC) exhibit systemic, brain and intrathecal inflammation, low CSF Aβ42, breakdown of the BBB, attention and short-term memory deficits, prefrontal white matter hyperintensities, damage to epithelial and endothelial barriers, tight junction and neural autoantibodies, and Alzheimer and Parkinson's hallmarks. The prefrontal white matter is a target of air pollution. We examined by light and electron microscopy the prefrontal white matter of MC dogs (n: 15, age 3.17±0.74 years), children and teens (n: 34, age: 12.64±4.2 years) versus controls. Major findings in MC residents included leaking capillaries and small arterioles with extravascular lipids and erythrocytes, lipofuscin in pericytes, smooth muscle and endothelial cells (EC), thickening of cerebrovascular basement membranes with small deposits of amyloid, patchy absence of the perivascular glial sheet, enlarged Virchow-Robin spaces and nanosize particles (20-48nm) in EC, basement membranes, axons and dendrites. Tight junctions, a key component of the neurovascular unit (NVU) were abnormal in MC versus control dogs (χ(2)<0.0001), and white matter perivascular damage was significantly worse in MC dogs (p=0.002). The integrity of the NVU, an interactive network of vascular, glial and neuronal cells is compromised in MC young residents. Characterizing the early NVU damage and identifying biomarkers of neurovascular dysfunction may provide a fresh insight into Alzheimer pathogenesis and open opportunities for pediatric neuroprotection.
authors.affiliation: The University of Montana, Missoula, MT 59812, USA; Universidad del Valle de México, Mexico City 04850, México. Electronic address: lilian.calderon-garciduenas@umontana.edu.
authors.forename: Lilian
authors.initials: L
authors.lastname: Calderón-Garcidueñas
authors.affiliation: Instituto Nacional de Pediatría, Mexico City 04530 México.
authors.forename: Rafael
authors.initials: R
authors.lastname: Reynoso-Robles
authors.affiliation: Universidad del Valle de México, Mexico City 04850, México.
authors.forename: Javier
authors.initials: J
authors.lastname: Vargas-Martínez
authors.affiliation: Universidad del Valle de México, Hermosillo, Sonora 83299, México.
authors.forename: Aline
authors.initials: A
authors.lastname: Gómez-Maqueo-Chew
authors.affiliation: Instituto Nacional de Pediatría, Mexico City 04530 México.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Pérez-Guillé
authors.affiliation: Mathematics Department, Boise State University, Boise, ID, USA.
authors.forename: Partha S
authors.initials: PS
authors.lastname: Mukherjee
authors.affiliation: Centro de Ciencias de la Atmósfera, Universidad Nacional Autónoma de México, Mexico City 04310, México.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Torres-Jardón
authors.affiliation: College of Sciences, University of Texas at San Antonio, San Antonio, TX, USA.
authors.forename: George
authors.initials: G
authors.lastname: Perry
authors.affiliation: Instituto Nacional de Pediatría, Mexico City 04530 México.
authors.forename: Angélica
authors.initials: A
authors.lastname: Gónzalez-Maciel
mesh_terms: D000293:Adolescent; D000397:Air Pollution / Q000009:adverse effects*; D000544:Alzheimer Disease / Q000139:chemically induced; D000818:Animals; D002648:Child; D002675:Child, Preschool; D004285:Dogs; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008800:Mexico; D046529:Microscopy, Electron, Transmission; D017397:Prefrontal Cortex / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D014505:Urban Population; D066127:White Matter / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure
keywords: Air pollution; Alzheimer; BBB; Children; Dogs; Endothelial damage; Nanosize particles; Neurovascular unit; PM(2.5); Tight junctions