Brain Res Mol Brain Res. 2005 Oct 31;140(1-2):73-85.
Genomic
regulation after CD40 stimulation in microglia: relevance to Alzheimer's
disease.
Ait-Ghezala G, Mathura VS, Laporte V, Quadros A, Paris D, Patel N, Volmar CH, Kolippakkam D, Crawford F, Mullan M.
The Roskamp Institute,
Key pathological processes in Alzheimer's disease (AD) include the accumulation
of amyloid beta peptide (Abeta) which, in excess,
triggers pathological cascades including widespread inflammation, partly
reflected by chronic microglial activation. It has
previously been suggested that CD40/CD40L interaction promotes AD like
pathology in transgenic mice. Thus, amyloid burden, gliosis
and hyperphosphorylation of tau
are all reduced in transgenic models of AD lacking functional CD40L. We
therefore hypothesized that cellular events leading to altered APP metabolism,
inflammation and increased tau phosphorylation
underlying these observations would be regulated at the genomic level. In the
present report, we used the Affymetrix (GeneChip) oligonucleotide
microarray U133A to gain insight into the global and
simultaneous transcriptomic changes in response to
microglia activation after CD40/CD40L ligation. As
expected, regulation of elements of the NF-kappaB
signaling, chemokine and B cell signaling pathways
was observed. Taken together, our data also suggest that CD40 ligation in human microglia specifically perturbs many
genes associated with APP processing.
Link:
Keywords: microglia, CD40, Alzheimer's disease, NF-kappa B, and Affymetrix