Microglial activation resulting from CD40-CD40L interaction after beta-amyloid stimulation

Alzheimer's disease (AD) has a substantial inflammatory component, and acti vated microglia may play a central role in neuronal degeneration, CD40 expr ession was increased on cultured microglia treated with freshly solublized amyloid-beta (A beta, 500 nanomolar) and on microglia from a transgenic mur ine model of AD (Tg APP(sw)). Increased tumor necrosis factor alpha product ion and induction of neuronal injury occurred when A beta-stimulated microg lia were treated with CD40 ligand (CD40L), Microglia from Tg APP(sw) mice d eficient for CD4OL demonstrated reduction in activation, suggesting that th e CD40-CD40L interaction is necessary for A beta-induced microglial activat ion. Finally, abnormal tau phosphorylation was reduced in Tg APP(sw) animal s deficient for CD40L, suggesting that the CD40-CD40L interaction is an ear ly event in AD pathogenesis.