Mapping Brain Cell Signals Offers New Targets for 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,” said Kim.

Reference: D’Oliveira Albanus R, Finan GM, Brase L, et al. Systematic analysis of cellular cross-talk reveals a role for SEMA6D-TREM2 regulating microglial function in Alzheimer’s disease. Sci Transl Med. 2025;17(809):eadx0027. doi: 10.1126/scitranslmed.adx0027

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