The vicious cycle governing the brain-immune system relationship in neurodegenerative diseases

For decades, neurodegenerative diseases were thought to be caused by the accumulation of toxic compounds, exacerbated by local inflammation, which together lead to neuronal loss and cognitive impairment . An additional factor that was long overlooked , is the role of the systemic immune system, which provides a defense mechanism against internal and external intruders in all bodily tissues. The evolving understanding of the life-long cross-talk between the CNS and the immune system led to an awareness of the function of systemic adaptive immunity in containing emerging destructive factors within the brain. . This includes harnessing of circulating myeloid cells to help the brain. However, as damage accumulates within the brain, the systemic immune system loses its protective capacity. Under such conditions, the dysregulated immune system becomes an escalating factor itself, thereby driving a vicious cycle that must be arrested.