Project Grant RF1AG077828

This $3.6 million project grant from the National Institute on Aging, part of the Department of Health and Human Services, will fund research at the Icahn School of Medicine at Mount Sinai directed at understanding the role of glial cell interactions surrounding amyloid plaques in the progression of Alzheimer's disease. As part of the Aging Research program (CFDA 93.866), the three-year award will support investigation of how deletion of the Plexin-B1 gene impacts glial network formation and the spread of amyloid aggregates. Researchers will analyze single-cell transcriptomic data from Alzheimer's patients and mouse models with and without Plexin-B1 to define co-regulated gene networks in reactive astrocytes and activated microglia associated with Plexin-B1 signaling. Functional studies using human induced pluripotent stem cell-derived astrocytes and primary astrocytes from Plexin-B1 mutant mice will explore the role of this gene in astrocyte activation in response to amyloid. Astrocyte-microglia co-cultures will also model glial interactions and amyloid response depending on Plexin-B1 status. In vivo work will assess the impact of Plexin-B1 deletion on glial networks, plaque deposition, neuronal function and cognitive performance in amyloid and tau mouse models of Alzheimer's at early and advanced stages.