Alzheimer's disease (AD) has a substantial inflammatory component, and activated microglia may play a central role in neuronal degeneration. CD40 expression was increased on cultured microglia treated with freshly solublized amyloid-β (Aβ, 500 nanomolar) and on microglia from a transgenic murine model of AD (Tg APP(sw),). Increased tumor necrosis factor α production and induction of neuronal injury occurred when Aβ-stimulated microglia were treated with CD40 ligand (CD40L). Microglia from Tg APP(sw) mice deficient for CD40L demonstrated reduction in activation, suggesting that the CD40-CD40L interaction is necessary for Aβ-induced microglial activation. Finally, abnormal tau phosphorylation was reduced in Tg APP(sw) animals deficient for CD40L, suggesting that the CD40-CD40L interaction is an early event in AD pathogenesis.
ASJC Scopus subject areas