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.