| First Author | Zhu Y | Year | 2011 |
| Journal | J Neurosci | Volume | 31 |
| Issue | 4 | Pages | 1355-65 |
| PubMed ID | 21273420 | Mgi Jnum | J:168546 |
| Mgi Id | MGI:4888985 | Doi | 10.1523/JNEUROSCI.3268-10.2011 |
| Citation | Zhu Y, et al. (2011) CD45 Deficiency Drives Amyloid-{beta} Peptide Oligomers and Neuronal Loss in Alzheimer's Disease Mice. J Neurosci 31(4):1355-1365 |
| abstractText | Converging lines of evidence indicate dysregulation of the key immunoregulatory molecule CD45 (also known as leukocyte common antigen) in Alzheimer's disease (AD). We report that transgenic mice overproducing amyloid-beta peptide (Abeta) but deficient in CD45 (PSAPP/CD45(-/-) mice) faithfully recapitulate AD neuropathology. Specifically, we find increased abundance of cerebral intracellular and extracellular soluble oligomeric and insoluble Abeta, decreased plasma soluble Abeta, increased abundance of microglial neurotoxic cytokines tumor necrosis factor-alpha and interleukin-1beta, and neuronal loss in PSAPP/CD45(-/-) mice compared with CD45-sufficient PSAPP littermates (bearing mutant human amyloid precursor protein and mutant human presenilin-1 transgenes). After CD45 ablation, in vitro and in vivo studies demonstrate an anti-Abeta phagocytic but proinflammatory microglial phenotype. This form of microglial activation occurs with elevated Abeta oligomers and neural injury and loss as determined by decreased ratio of anti-apoptotic Bcl-xL to proapoptotic Bax, increased activated caspase-3, mitochondrial dysfunction, and loss of cortical neurons in PSAPP/CD45(-/-) mice. These data show that deficiency in CD45 activity leads to brain accumulation of neurotoxic Abeta oligomers and validate CD45-mediated microglial clearance of oligomeric Abeta as a novel AD therapeutic target. |
