Alzheimer's disease (AD) is the most prevalent age-related neurodegenerative disease in the United States. More than 90% of cases are idiopathic and there is growing consensus that environmental factors interact with genes of susceptibility to influence the age of onset and progression of this disease. Recent epidemiological studies have reported a positive correlation between exposure to traffic-related air pollution and the occurrence of the hallmark clinical characteristics of AD, including increased expression of pro-inflammatory markers in the brain, diffuse amyloid plaques, neuronal cell loss, and impaired cognition. We hypothesize that traffic- related air pollution emitted from motor vehicles triggers inflammatory responses in the brain that initiate or accelerate the progression of AD. To test this, we will use a unique animal model: the TgF344 rat, which expresses human genes that confer susceptibility to AD. We will expose male and female TgF344 rats and their wildtype littermates to polluted air sampled directly from the Caldecott tunnel in the San Francisco area beginning at postnatal day 28 to up to 12 months of age. Caldecott tunnel air will be delivered to animals housed in a portable vivarium parked adjacent to the tunnel. Control animals will be exposed to clean filtered air. Caldecott tunnel air will be collected every three weeks for gas and particle chemical characterization, and both Caldecott tunnel air and clean filtered air will be monitored continuously for particle size distribution and concentration. Learning and memory as well as neuroinflammation and AD-like pathology will be assessed in animals at 3, 6, 9 and 12 months of age. These studies will provide proof-of-concept data identifying functionally relevant interactions between AD-linked genetic susceptibilities and a ubiquitous environmental risk factor.
Epidemiological studies have associated traffic-related air pollution with an increased risk for Alzheimer's disease (AD); however, a causal relationship has yet to be demonstrated. The goal of this project is to test the hypothesis that exposure to vehicular emissions triggers inflammatory responses in the brain that initiate or accelerate the progression of AD pathology and cognitive dysfunction depending upon sex, age, and genetic susceptibility. These studies are needed to corroborate human studies linking traffic-related air pollution exposure to increased risk for AD. The confirmation of traffic-related air pollution as a environmental risk factor for AD will provide data needed to support the mobilization of resources by public health officials to protect at-risk populations.
| Voorhees, Jaymie R; Rohlman, Diane S; Lein, Pamela J et al. (2016) Neurotoxicity in Preclinical Models of Occupational Exposure to Organophosphorus Compounds. Front Neurosci 10:590 |
