Boosting peripheral immunity to fight neurodegeneration in the brain

Reciprocal communication between the brain and the immune system is essential for maintaining lifelong brain function. This interaction is mediated, at least in part, by immune cells recruited from both the circulation and niches at the borders of the brain. Here, we describe how immune exhaustion and senescence, even if not primary causative factors, can accelerate neurodegenerative diseases. We emphasize the role of a compromised peripheral immune system in driving neurodegeneration and discuss strategies for harnessing peripheral immunity to effectively treat neurodegenerative diseases, including the underlying mechanisms and opportunities for clinical translation. Specifically, we highlight the potential of boosting the immune system by blocking inhibitory checkpoint molecules to harness reparative immune cells in helping the brain to fight against neurodegeneration.