Science · 1999 · 354 citations · 27 references
Life SciencesNeurobiologyNeuroscienceInflammationNeurodegenerationNeuroimmunologyAlzheimer DiseaseMicroglia BiologyNeurodegeneration MechanismsNeurodegenerative DiseasesNeurodegenerative DisordersNeuroinflammationAlzheimer Disease NeuroimmunologyAmyloid-beta-induced NeurotoxicityCd40l SignalingMicroglia ActivationMicroglial Responses To InjuryMurine ModelsNeuroinflammation In Alzheimer DiseaseTau Hyperphosphorylation
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-beta (Abeta, 500 nanomolar) and on microglia from a transgenic murine model of AD (Tg APPsw). Increased tumor necrosis factor alpha production and induction of neuronal injury occurred when Abeta-stimulated microglia were treated with CD40 ligand (CD40L). Microglia from Tg APPsw mice deficient for CD40L demonstrated reduction in activation, suggesting that the CD40-CD40L interaction is necessary for Abeta-induced microglial activation. Finally, abnormal tau phosphorylation was reduced in Tg APPsw animals deficient for CD40L, suggesting that the CD40-CD40L interaction is an early event in AD pathogenesis.
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