Evaluating the Role of the TDP-43 Protein in Alzheimer's Disease Pathogenesis

Project Summary

TDP-43 proteins abnormally accumulate in the brain of up to 70% of people with Alzheimer’s disease and are characterized by worse memory and greater brain atrophy compared to those with Alzheimer’s lacking TDP-43 pathology. This proposal aims to characterize the role of TDP-43 dysfunction in the pathogenesis of Alzheimer’s by evaluating: 1) whether TDP-43 dysfunction exacerbates behavior and pathological Alzheimer’s phenotypes, as well as induces neuronal loss in an Alzheimer’s mouse model, and 2) the relationships between Alzheimer’s pathologies and TDP-43 dysfunction in Alzheimer’s human brains. 

These studies are expected to also highlight the importance of TDP-43 pathology in therapeutic target and biomarker design and in participant evaluations during clinical trials.