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
- The University of Montana, Missoula, MT 59812 (United States)
- Instituto Nacional de Pediatría, Mexico City 04530 México (Mexico)
- Universidad del Valle de México, Mexico City 04850, México (Mexico)
- Universidad del Valle de México, Hermosillo, Sonora 83299, México (Mexico)
- Mathematics Department, Boise State University, Boise, ID (United States)
- Centro de Ciencias de la Atmósfera, Universidad Nacional Autónoma de México, Mexico City 04310, México (Mexico)
- College of Sciences, University of Texas at San Antonio, San Antonio, TX (United States)
Millions of urban children are chronically exposed to high concentrations of air pollutants, i.e., fine particulate matter (PM{sub 2.5}) 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 Aβ{sub 42,} 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 (20–48 nm) 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{sup 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. - Highlights: • The prefrontal white matter is a target of air pollution. • Tight junctions, key neurovascular unit elements, are abnormal in young urbanites. • Identifying neurovascular dysfunction biomarkers is key for pediatric neuroprotection. • Early characterization of NVU damage may provide a fresh insight into AD pathogenesis.
- OSTI ID:
- 22687732
- Journal Information:
- Environmental Research, Vol. 146; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0013-9351
- Country of Publication:
- United States
- Language:
- English
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