An immune system-activating cancer medication improves cognitive performance and memory and reduces pathology in mouse models of Alzheimer's disease, reports a new paper published online in Nature Medicine this week. The study identifies immune-checkpoint blockade as a potential therapeutic approach for Alzheimer's disease and, possibly, for other neurodegenerative diseases.
Immune checkpoints are pathways in immune cells that can either activate or suppress immune responses. Programmed death-1 (PD-1) blockers are a class of cancer medications, recently approved by the US Food and Drug Administration, that block the PD-1 immune-checkpoint pathway. This activates immune cells and enables them to attack cancer cells.
In the study, Michal Schwartz and colleagues treated small groups of transgenic mice that develop hallmarks of Alzheimer’s disease, including the deposition of toxic amyloid-beta (Aβ) plaques in the brain and progressive memory impairment. They find that mice treated twice with PD-1 blockers over three days show improved memory performance, reduced brain pathology and reduced inflammation one month after treatment, compared to transgenic mice that received either placebo or no treatment. They observed an even more pronounced improvement in learning, memory and pathology in mice that received two treatment sessions over two consecutive months. The authors suggest that PD-1 blockade promotes the recruitment of protective immune cells into the brain, which may subsequently promote clearance of toxic Aβ plaques.