Microglial activation resulting from CD40-CD40L interaction after beta-amyloid stimulation.
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.
Tan
J
J
The Roskamp Institute, University of South Florida, 3515 East Fletcher Avenue, Tampa, FL 33613, USA.
Town
T
T
Paris
D
D
Mori
T
T
Suo
Z
Z
Crawford
F
F
Mattson
M P
MP
Flavell
R A
RA
Mullan
M
M
D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D019013:CD40 Antigens / Q000096:biosynthesis / Q000378:metabolism*; D023201:CD40 Ligand; D016923:Cell Death; D002478:Cells, Cultured; D007371:Interferon-gamma / Q000494:pharmacology; D007378:Interleukins / Q000494:pharmacology; D008024:Ligands; D008562:Membrane Glycoproteins / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D009474:Neurons / Q000166:cytology; D010446:Peptide Fragments / Q000494:pharmacology; D010766:Phosphorylation; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000494:pharmacology; D016875:tau Proteins / Q000378:metabolism
D016229:Amyloid beta-Peptides; D019013:CD40 Antigens; D007378:Interleukins; D008024:Ligands; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D023201:CD40 Ligand; D007371:Interferon-gamma