Federal Project Grant Award Summary

Case Western Reserve University's Office of Research Administration has been awarded $691,999 by the National Institute on Aging under the Aging Research program (CFDA 93.866) to conduct a comprehensive investigation of tau protein seeding mechanisms in the human brain. The award, issued on March 15, 2026, with a completion date of November 30, 2030, will support research that identifies the distribution, quantity, and biochemical characteristics of tau seeds across diseased and healthy human brains across various age groups. The research team will utilize ultrasensitive real-time quaking-induced conversion (RT-QUIC) seed amplification assays to characterize tau seeds and develop a detailed understanding of how post-translational modifications, co-pathologies, and inflammatory responses modulate tau seeding in neurodegenerative diseases including Alzheimer's disease, frontotemporal lobar degeneration, and primary age-related tauopathy.

The project employs multifaceted analytical approaches including seed detection methodologies, biochemical assays, immunomapping, structural profiling, proteomic analysis, single-nucleus RNA sequencing, and spatial transcriptomic techniques to establish cellular states within the brain microenvironment across disease stages. A significant focus of the research involves elucidating the roles of myeloid and glial cells in tau seed propagation and clearance through investigation of inflammatory responses and reactive oxygen species mechanisms. The research outputs will directly contribute to identifying critical therapeutic targets and advancing understanding of the earliest tau misfolding events in human neurodegeneration.