Abstract
Accumulating epidemiological evidence supports that chronic exposure to ambient fine particular matters of <2.5 μm (PM2.5) predisposes both children and adults to Alzheimer's disease (AD) and age-related brain damage leading to dementia. There is also experimental evidence to show that PM2.5 exposure results in early onset of AD-related pathologies in transgenic AD mice and development of AD-related and age-related brain pathologies in healthy rodents. Studies have also documented that PM2.5 exposure causes AD-linked molecular and cellular alterations, such as mitochondrial dysfunction, synaptic deficits, impaired neurite growth, neuronal cell death, glial cell activation, neuroinflammation, and neurovascular dysfunction, in addition to elevated levels of amyloid β (Aβ) and tau phosphorylation. Oxidative stress and the oxidative stress-sensitive TRPM2 channel play important roles in mediating multiple molecular and cellular alterations that underpin AD-related cognitive dysfunction. Documented evidence suggests critical engagement of oxidative stress and TRPM2 channel activation in various PM2.5-induced cellular effects. Here we discuss recent studies that favor causative relationships of PM2.5 exposure to increased AD prevalence and AD- and age-related pathologies, and raise the perspective on the roles of oxidative stress and the TRPM2 channel in mediating PM2.5-induced predisposition to AD and age-related brain damage.