Therapeutic targeting of neuroimmune mechanisms in neurodegeneration.

Effective treatments for age-related chronic neurodegenerative diseases such as Alzheimer's disease remain limited, in part because the molecular drivers of cognitive decline are still not fully understood. Human genetic studies, together with detailed analysis of disease pathology, indicate that the immune system has an important influence on disease progression. Research to date has focused largely on microglia - specialized innate immune cells that reside within the central nervous system (CNS) - as functional studies combined with deep transcriptional profiling have improved our understanding of this innate immune cell type in neurodegeneration and have identified several potential therapeutic targets. Increasing evidence now shows that microglia coordinate diverse CNS and peripheral cell populations to shape disease outcomes. In this Review, we discuss these neuroimmune interactions, which reveal a more intricate framework for how the central and peripheral immune systems may influence neurodegeneration. These insights could redirect future drug discovery efforts towards immune targets that complement existing therapies aimed at core pathological features. We also outline how this knowledge suggests new therapeutic strategies and highlight a critical need for disease-specific neuroimmune biomarkers.