Researchers at the USC Mark and Mary Stevens Neuroimaging and Informatics Institute at the Keck School of Medicine of USC announced on Apr. 9 that they have received a major grant from the National Institutes of Health to study how specific neuron loss in the hippocampus contributes to cognitive impairment in Alzheimer's disease.
The project aims to address why certain neurons in the brain region responsible for memory formation are more vulnerable than others, with hopes of identifying early changes that could lead to better treatments for Alzheimer’s disease. More than six million Americans are affected by Alzheimer’s, a number expected to nearly double by 2050.
Michael S. Bienkowski, PhD, assistant professor at the Keck School of Medicine and principal investigator, said: "Alzheimer's doesn't damage the brain uniformly. Even within the same brain region, some neurons deteriorate rapidly while others remain relatively intact. This project is designed to model how cellular and molecular changes to these neurons and their connections begin to disrupt the hippocampal network and lead to dysfunction." The five-year NIH R01 award will support development of a cell type-specific multiscale model that connects information from individual cells up through whole-brain networks.
The research builds on Bienkowski's previous work developing a gene expression atlas for distinct neuron populations in the hippocampus. The team will use advanced molecular imaging, three-dimensional circuit reconstruction, and computational modeling techniques on both mouse models and donated human tissue. Their goal is to pinpoint which cell types show early signs of stress or damage before neuron death occurs.
Bienkowski said: "This multiscale approach allows us to connect changes that occur in different parts of the hippocampus at different progressive timepoints... It provides a virtual testbed for safely and rapidly evaluating new disease treatment targets." A key aspect is simulating how protecting or restoring certain neuron types might stabilize memory-related networks as Alzheimer's progresses.
Arthur W. Toga, PhD, director of Stevens INI at USC, said: "This work demonstrates how integrating large-scale data, advanced imaging, and computational modeling can transform our understanding of neurodegenerative disease... By pinpointing which neurons matter most and when they become vulnerable, this research lays essential groundwork for more targeted and effective treatments." All models developed through this project will be made openly available so other scientists can build upon them.
