NIH Reporter #11237123

Characterizing novel Mixed Etiology Dementia models compromised for TDP-43 function

Research project to understand TDP-43 pathology in mixed etiology dementias, develop mouse models exhibiting multiple pathologies, and identify therapeutic targets for Alzheimer's and related dementias.

Description

This project focuses on understanding the role of TDP-43 pathology in neurodegenerative diseases, particularly in mixed etiology dementias such as Alzheimer’s Disease with TDP-43 pathology (AD-TDP) and frontotemporal dementia (FTD). The research aims to elucidate the mechanisms of TDP-43 in the pathological conversion and spreading of tau protein, and to develop models of dementia that exhibit Aβ, tau, and TDP-43 pathologies. The study involves characterizing mouse models with hippocampal injections of AAV vectors encoding Tau4R with mutations, in mice lacking TDP-43 in forebrain neurons, and evaluating tauopathy, neuron loss, and microglia signatures. The findings are expected to identify novel therapeutic targets for AD/ADRDs.

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