Air Pollution and vulnerability to Alzheimer-like neurodegeneration in mice

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DESCRIPTION (provided by applicant): Air pollution may accelerate brain aging. Epidemiological studies of the middle-age have shown accelerated cognitive decline in association with local differences in air pollution (Chen & Schwartz 2010), while brains of young adults from a highly polluted Mexican city had premature deposits of diffuse amyloid and glial inflammatory activation which were greater in apoE4 carriers (Block & Calderon-Garciduenas 2009). Corresponding rodent models with defined exposure to traffic-generated nano-sized particulate material (nPM) have shown glial inflammatory changes. Our pilot data show that exposure to nPM for 10 weeks activated glia and altered neuronal glutamatergic receptors in vivo and in vitro. We propose to analyze effects of nPM on glial inflammation, amyloidogenesis, and neurodegeneration in J20-ADtg mice and in triple transgenic AD mice (3xTg-AD), which has more extensive AD-like neuropathology. We will also test the hypotheses that nPM promotes Abeta42 production and exacerbates Abeta42-induced toxicity using in vitro models. PUBLIC HEALTH RELEVANCE: These novel studies will use mouse models to define the neurodegenerative pathways of urban airborne nano-sized particulate matter (nPM). We will evaluate the hypothesis that nPM causes neural damage through shared pathways with amyloid-beta. Identification of mechanisms and of relevant biomarkers in nPM toxicology is essential for development of broad-spectrum interventions.