| First Author | Tan J | Year | 2002 |
| Journal | Nat Neurosci | Volume | 5 |
| Issue | 12 | Pages | 1288-93 |
| PubMed ID | 12402041 | Mgi Jnum | J:80429 |
| Mgi Id | MGI:2445861 | Doi | 10.1038/nn968 |
| Citation | Tan J, et al. (2002) Role of CD40 ligand in amyloidosis in transgenic Alzheimer's mice. Nat Neurosci 5(12):1288-93 |
| abstractText | We have shown that interaction of CD40 with CD40L enables microglial activation in response to amyloid-beta peptide (Abeta), which is associated with Alzheimer's disease (AD)-like neuronal tau hyperphosphorylation in vivo. Here we report that transgenic mice overproducing Abeta, but deficient in CD40L, showed decreased astrocytosis and microgliosis associated with diminished Abeta levels and beta-amyloid plaque load. Furthermore, in the PSAPP transgenic mouse model of AD, a depleting antibody against CD40L caused marked attenuation of Abeta/beta-amyloid pathology, which was associated with decreased amyloidogenic processing of amyloid precursor protein (APP) and increased circulating levels of Abeta. Conversely, in neuroblastoma cells overexpressing wild-type human APP, the CD40-CD40L interaction resulted in amyloidogenic APP processing. These findings suggest several possible mechanisms underlying mitigation of AD pathology in response to CD40L depletion, and validate the CD40-CD40L interaction as a target for therapeutic intervention in AD. |
