Advanced imaging exposes breakdown in brain cell communication linked to Alzheimer’s

Research led by The Ohio State University Wexner Medical Center and College of Medicine explores the ways brain cells communicate, revealing fresh insight into the progression of Alzheimer’s disease.

A multidisciplinary team used advanced imaging and computational modeling to analyze the “crosstalk” between neurons and their supporting glial cells in the human brain. This approach highlights the brain’s interconnected cellular network.

“By mapping these cell interactions at the molecular level, we identified key pathways that could be pivotal in both the onset and progression of neurodegeneration,” said study co-author Oscar Harari, PhD, director of the Division of Neurogenetics and director of the Center for Neurobiology of Aging and Resiliency at The Ohio State University Neuroscience Research Institute.

Study findings are published in Science Translational Medicine.

“This insight is critical for developing effective treatments, as ‘cellular crosstalk’ may serve as an attractive molecular target for drug development. Many of these cell-to-cell communication pathways include proteins at the cell membrane, which are often regarded as promising targets for therapeutic intervention,” said Harari, who is also the Helen C. Kurtz Associate Professor of Neurology at Ohio State.

Harari, who joined Ohio State in early 2024, completed the manuscript for the research he started while at the Washington University School of Medicine. He collaborated equally with study co-author Tae-Wan Kim, PhD, associate professor of Pathology and Cell Biology at Columbia University Vagelos College of Physicians and Surgeons in New York.

Our research shows that Alzheimer’s is not only driven by plaques and tangles, but also by a breakdown in communication between brain cells. By uncovering the SEMA6D–TREM2 crosstalk pathway, we reveal a new way to enhance the amyloid-clearing functions of microglia and potentially slow Alzheimer’s progression.”

Tae-Wan Kim, PhD, associate professor of Pathology and Cell Biology, Columbia University Vagelos College of Physicians and Surgeons, New York

The study included investigators from The Ohio State University Comprehensive Cancer Center, as well as collaborators from Australia, South Korea, Massachusetts General Hospital, Harvard Medical School, Indiana University School of Medicine, and the Dominantly Inherited Alzheimer Network.

This research is supported by funding from the National Institute on Aging; National Institute of Neurological Disorders and Stroke; Department of Defense; Chan Zuckerberg Initiative; Alzheimer’s Association; German Center for Neurodegenerative Diseases; Raul Carrea Institute for Neurological Research; Japan Agency for Medical Research and Development; Korea Health Industry Development Institute; Spanish Institute of Health Carlos III; Canadian Institutes of Health Research; Canadian Consortium of Neurodegeneration and Aging; Brain Canada Foundation; Fonds de Recherche du Québec – Santé; Arizona Department of Health Services; Arizona Biomedical Research Commission and Michael J. Fox Foundation for Parkinson’s Research.