Clinical Relevance of the Linkage between Environmental Toxicant Exposures and Alzheimers Disease and Related Dementias (R01 Clinical Trial Not Allowed)

There is consensus that environmental toxicants are a risk factor for AD/ADRD, but causality has been largely elusive. While human studies demonstrating an association of AD/ADRD with toxicant exposures are relatively abundant, there is a clear unmet need for more mechanistic research to support or refute the clinical relevance and the biological plausibility of an impact on disease initiation, progression, or modification. This is especially important for understanding the potentially modifiable causes of racial and socioeconomic inequities. The RFA will encourage neuroscientists to conduct mechanistic AD/ADRD research on the actions of neurotoxicants on the nervous system. The scope of research includes but is not limited to in silico modeling, in vitro assay development to correlate chemical exposure to AD/ADRD biology, and in vivo studies on the modification of known AD/ADRD targets by neurotoxicants of concern, and conversely, whether known targets for these neurotoxins play a role in the etiology of AD/ADRD. The development and validation of neuropathological, neurophysiological, and neurobehavioral animal models that simulate potential toxicant exposures in humans would be one goal, and when possible, these studies will include comparisons of exposures across the lifespan.