Microglial Activation Resulting from CD40-CD40L Interaction After β-Amyloid Stimulation

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Science  17 Dec 1999:
Vol. 286, Issue 5448, pp. 2352-2355
DOI: 10.1126/science.286.5448.2352

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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 APPsw). 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 APPsw 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 APPsw animals deficient for CD40L, suggesting that the CD40-CD40L interaction is an early event in AD pathogenesis.

  • * These authors contributed equally to this work.

  • To whom correspondence should be addressed. E-mail: mmullan{at}

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