Role of Activated Glia and of Glial Cytokines in Alzheimer's Disease: A Review.

We review the role of activated microglia and activated astrocytes, and of glia-derived cytokines and other molecules, in the pathogenesis and pathophysiology of Alzheimer's disease. Activated microglia overexpressing the potent immune-response cytokine interleukin-1, and activated astrocytes over-expressing the neurotrophic cytokine S100β, are near-constant components of neuritic plaques in Alzheimer's disease, and are frequent components of early, non-neuritic, amyloid deposits. The known biological activities of these two cytokines suggest an orchestrating effect on the complex cellular and molecular interactions that drive plaque progression. Furthermore, findings in brains of patients dying with conditions known to predispose to Alzheimer's disease suggest that activation of glia and overexpression of glial cytokines are early events in Alzheimer pathogenesis. These results suggest that therapeutic intervention directed toward interrupting the driving immunological processes in Alzheimer's disease might slow or arrest progression of clinical disease.