Harnessing the Brain's Cleanup Crew: A New Frontier in Alzheimer's Treatment, Study Reveals
For more than three decades, scientists have been racing to stop Alzheimer's disease by removing amyloid beta plaques-sticky clumps of toxic protein that accumulate in the brain. Now, a new Northwestern Medicine study suggests a promising alternative: enhancing the brain’s own immune cells to clear these plaques more effectively.
The findings could reshape the future of Alzheimer’s treatments, shifting the focus from simply removing plaques to harnessing the brain’s natural defenses. The paper is published in Nature Medicine. By analyzing donated brain tissue from deceased people with Alzheimer’s disease who received amyloid-beta immunization and comparing it to those who did not, the scientists found that when these treatments work, the brain’s immune cells (called microglia) don’t just clear plaques — they also help restore a healthier brain environment.
The study included six control brains that had no neurologic disease; six brains with Alzheimer’s disease that had not been treated with any immunization drug; and 13 brains that had been vaccinated with amyloid beta. Of those 13, seven had high levels of amyloid-plaque clearance in the brain while the other six had limited amounts of clearance.The scientists then compared the immune cells in the brains between those two groups.
"Our study is highly novel because we had the rare opportunity to analyze one of the largest post-mortem brain cohorts of Alzheimer's patients treated with amyloid-targeting drugs — similar to those now approved by the FDA for Alzheimer's disease," said lead author Lynn van Olst.
"This allowed us to investigate the brain mechanisms that determine why some individuals respond well to these treatments and successfully clear toxic amyloid-beta, while others do not. We found that brain immune cells play a crucial role in this process and identified the molecular genetic factors that drive these differences."
Ref: van Olst, L., Simonton, B., Edwards, A.J. et al. Microglial mechanisms drive amyloid-β clearance in immunized patients with Alzheimer’s disease. Nat Med (2025). https://doi.org/10.1038/s41591-025-03574-1
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