TDP-43 Mislocalization in Aging and Neurodegeneration

Gene mutations and aging work together to cause neurodegenerative diseases, yet we know little about how genetic- and age-related changes interact at the molecular and cellular levels to drive disease. This project addresses the intersection of aging and genetics using complementary genomic, biochemical, and proteomic approaches in human iPSC-derived neurons, using an in vivo killifish model of aging with an initial focus on TDP-43’s role in proteostasis, a gene associated with ALS/FTD and other neurodegenerative diseases. Any findings could have important implications for understanding how aging increases risk for neurodegenerative diseases.

This project was selected for the second phase of the Collaborative Pairs RFA.