Targeting Beneficial Innate Immunity in Alzheimer’s by IRAK-M Deletion

A defining feature of Alzheimer’s disease is brain accumulation of toxic plaques that induce memory loss. In the healthy brain, innate immune cells are protective; however, in Alzheimer patients’ brains, these cells fail to prevent plaque formation. Innate immune cells express a molecule named IRAK-M that ensures immune responses to invading bacteria and viruses are kept under tight control. Yet, this type of immune response is dysfunctional in the Alzheimer patient brain. Our hypothesis is that ‘re-balancing’ the brain’s immune response by blocking IRAK-M will enable plaque clearance. With Cure Alzheimer’s Fund support over this past year, we now report that removal of the anti-inflammatory IRAK-M gene from mice that develop amyloid plaques with age restores deficits in learning and memory. Thus far, this project has provided crucial data on the role of IRAK-M and the innate immune system in Alzheimer’s disease, and we seek an additional year of funding to expand on this work to deeply understand the nature of this beneficial brain immune response. This important work represents a major step toward developing a novel immunological therapy for this devastating disorder of the mind.