New Protein Interaction Map Illuminates Breakdown of Brain Cell Communication in Alzheimer's Disease

A groundbreaking study conducted by researchers at the Icahn School of Medicine at Mount Sinai has provided unprecedented insights into the complex interactions between brain cells in Alzheimer's disease. The research maps intricate protein networks within the brain, revealing how communication pathways deteriorate during disease progression and offering new avenues for therapeutic intervention.

Published in the journal Cell, the study analyzed protein activity in brain tissues from nearly 200 individuals, both with and without Alzheimer's. Using advanced proteomics technology, scientists quantified over 12,000 proteins, constructing comprehensive networks that highlight where cellular communication fails. The findings emphasize that the disruption of communication between neurons and glial cells—especially astrocytes and microglia—is a central feature of Alzheimer's pathology.

One key discovery is the identification of the protein AHNAK, predominantly found in astrocytes, which increases as Alzheimer's progresses and correlates with toxic proteins like amyloid beta and tau. Experimental reduction of AHNAK in human brain cell models led to decreased tau levels and improved neuronal function, suggesting that targeting AHNAK could be a promising therapeutic strategy.

The study also uncovered a broader network of over 300 proteins rarely studied in relation to Alzheimer's, expanding potential research directions. It further demonstrated that genetic factors like the APOE4 gene influence these protein networks, affecting disease pathways. The researchers employed an unsupervised analytical approach, which allows exploration of complex protein interactions without pre-existing assumptions.

Overall, this research shifts the understanding of Alzheimer's from a focus solely on toxic protein accumulation to a broader view of how brain cell communication breaks down. Dr. Bin Zhang stated that restoring these communication pathways could be key to developing effective treatments for the disease.

The comprehensive proteomic data is publicly accessible, enabling scientists worldwide to advance this important field. This study marks a significant step towards understanding the systemic failure of brain networks in Alzheimer's and highlights new potential targets for therapeutic development.

For detailed findings, visit the original study in Cell: DOI: 10.1016/j.cell.2025.08.038. Source: https://medicalxpress.com/news/2025-09-protein-interaction-brain-cell-communication.html