Microglial activation resulting from CD40-CD40l interaction after β- amyloid stimulation

Jun Tan, Terrence Town, Daniel Paris, Takashi Mori, Zhiming Suo, Fiona Crawford, Mark P. Mattson, Richard A. Flavell, Michael Mullan

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2352-2355
Number of pages4
JournalScience
Volume286
Issue number5448
DOIs
StatePublished - Dec 17 1999
Externally publishedYes

ASJC Scopus subject areas

  • General

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