Northwestern Medicine researchers have proposed a novel approach to treating Alzheimer's disease by enhancing the brain's own immune cells, known as microglia, to more effectively clear amyloid beta plaques. This study could shift the focus of future Alzheimer's treatments from simply removing plaques to leveraging the brain’s natural defenses.
The study, published in Nature Medicine on March 6, is the first to employ spatial transcriptomics on human clinical-trial brains with Alzheimer’s disease. This technique allows scientists to locate specific gene activity within tissue samples.
Corresponding author David Gate from Northwestern University Feinberg School of Medicine emphasized that current FDA-approved antibody treatments for Alzheimer's are controversial due to their modest benefits and potential side effects. "These drugs stimulate the immune cells of the brain to remove amyloid beta, but we believe that the data in our publication can be utilized to make these drugs work even better," Gate stated.
By analyzing donated brain tissue from individuals with Alzheimer’s who received amyloid-beta immunization compared to those who did not, researchers discovered that microglia not only clear plaques but also help restore a healthier brain environment. However, microglia effectiveness varies depending on several factors such as brain region and type of immunization. Certain genes like TREM2 and APOE become more active in response to treatment, aiding plaque removal.
Gate addressed a key question regarding whether immune cells remain in an amyloid-removal mode indefinitely. He explained, “The answer we found is no, they can remove the amyloid and then go back to being good and appear to actually help the brain heal.”
The study supports the amyloid cascade hypothesis which suggests clearing plaques before triggering tau pathology—the main driver of cognitive decline—can prevent further damage. Gate highlighted this by stating that early treatment might stop tau spread before it begins.
Lead author Lynn van Olst noted that their research allowed them "to investigate the brain mechanisms that determine why some individuals respond well" while others do not. The findings identified crucial molecular genetic factors influencing these differences.
Funding for this research came from various sources including grants from the National Institutes of Health National Institutes of Aging R01 grant AG078713 and others.