The $745,092 federal Project Grant awarded by the National Institute on Aging (CFDA 93.866 - Aging Research) will fund research conducted by the University of Virginia to elucidate the role of RNA modification, specifically N6-methyladenosine (m6A), in the pathogenesis of Alzheimer's disease and related tauopathies.
The research aims to: 1) Decode the epitranscriptomic profiles impacted by tau pathology using m6A DART-seq, 2) Determine the role of RNA methylation in Alzheimer's disease pathogenesis using 3D neuron-glial brain assembloids, and 3) Evaluate the therapeutic impact of inhibiting excessive RNA methylation in a humanized tau and APP double transgenic mouse model of Alzheimer's disease. The findings from this research are expected to provide new insights into the molecular mechanisms underlying neurodegenerative diseases at the epitranscriptomic level, potentially leading to new therapeutic strategies.