Federal Grant Award Summary

Yale University received a $507,741 Project Grant from the National Institute on Aging under the Aging Research program (CFDA 93.866), awarded August 1, 2026, with completion scheduled for July 31, 2028. This research project delivers scientific investigation into the earliest molecular mechanisms of sporadic Alzheimer's disease, specifically defining the spatial relationships between early endosomal abnormalities, amyloid pathology, and tau hyperphosphorylation. The research employs a multiscale approach utilizing human postmortem tissue across Braak disease stages, perfusion-fixed rhesus macaque brain tissue, and human induced pluripotent stem cell (hiPSC)-derived neurons, including SORL1-deficient lines that model genetic risk factors for endolysosomal dysfunction.

The project outputs include quantitative immunofluorescence analyses mapping phosphorylated tau at threonine 217 (pT217tau), endosomal enlargement, and amyloid-beta 42 (Aβ42) across vulnerable brain regions, as well as mechanistic validation data from hiPSC neuronal models. These research deliverables are designed to advance understanding of preclinical Alzheimer's disease pathology and support development of early diagnostic tools and therapeutic interventions targeting the convergence of soluble tau phosphorylation, amyloid precursor protein processing, and endosomal dysfunction in disease progression.