CD45 Deficiency Drives Amyloid-β Peptide Oligomers and Neuronal Loss in Alzheimer's Disease Mice

• DOI: 10.1523/jneurosci.3268-10.2011
• Publication Date: 2011-01-27T18:19:30Z
• Authors: Yuyan Zhu; Huayan Hou; Kavon Rezai-Zadeh; Brian Giunta; Amanda Ruscin; Carmelina Gemma; JingJi Jin; Natasa Dragicevic; Patrick Bradshaw; Suhail Rasool; Charles G. Glabe; Jared Ehrhart; Paula Bickford; Takashi Mori; Demian Obregon; Terrence Town; Jun Tan
• Keywords: Proinflammatory cytokine; Amyloid (mycology)

Converging lines of evidence indicate dysregulation the key immunoregulatory molecule CD45 (also known as leukocyte common antigen) in Alzheimer's disease (AD). We report that transgenic mice overproducing amyloid-β peptide (Aβ) but deficient ( PSAPP/CD45 −/− mice) faithfully recapitulate AD neuropathology. Specifically, we find increased abundance cerebral intracellular and extracellular soluble oligomeric insoluble Aβ, decreased plasma microglial neurotoxic cytokines tumor necrosis factor-α interleukin-1β, neuronal loss compared with CD45-sufficient PSAPP littermates (bearing mutant human amyloid precursor protein presenilin-1 transgenes). After ablation, vitro vivo studies demonstrate an anti-Aβ phagocytic proinflammatory phenotype. This form activation occurs elevated Aβ oligomers neural injury determined by ratio anti-apoptotic Bcl-xL to proapoptotic Bax, activated caspase-3, mitochondrial dysfunction, cortical neurons mice. These data show deficiency activity leads brain accumulation validate CD45-mediated clearance a novel therapeutic target.