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Science 17 December 1999:
Vol. 286. no. 5448, pp. 2352 - 2355
DOI: 10.1126/science.286.5448.2352
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Reports

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

Jun Tan, 1* Terrence Town, 1* Daniel Paris, 1* Takashi Mori, 1 Zhiming Suo, 1 Fiona Crawford, 1 Mark P. Mattson, 2 Richard A. Flavell, 3 Michael Mullan 1dagger

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.

1 The Roskamp Institute, University of South Florida, 3515 East Fletcher Avenue, Tampa, FL 33613, USA.
2 Sanders-Brown Research Center on Aging and Department of Anatomy and Neurobiology, University of Kentucky, Lexington, KY 40536, USA.
3 Howard Hughes Medical Institute, Yale University School of Medicine, 310 Cedar Street, New Haven, CT 06520, USA.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: mmullan{at}com1.med.usf.edu

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