| First Author | Bruce-Keller AJ | Year | 2011 |
| Journal | Neurobiol Dis | Volume | 44 |
| Issue | 3 | Pages | 317-26 |
| PubMed ID | 21798347 | Mgi Jnum | J:178563 |
| Mgi Id | MGI:5299281 | Doi | 10.1016/j.nbd.2011.07.012 |
| Citation | Bruce-Keller AJ, et al. (2011) Cognitive impairment in humanized APPxPS1 mice is linked to Abeta(1-42) and NOX activation. Neurobiol Dis 44(3):317-26 |
| abstractText | Cognitive impairment in Alzheimer's disease (AD) is strongly associated with both extensive deposition of amyloid beta peptides and oxidative stress, but the exact role of these indices in the development of dementia is not clear. This study was designed to determine the relationship between cognitive impairment, activation of the free radical producing enzyme NADPH oxidase (NOX), and progressive changes in Abeta deposition and solubility in humanized APPxPS1 knock-in mice of increasing age. Data show that cognitive performance and expression of key synaptic proteins were progressively decreased in aging APPxPS1 mice. Likewise, NOX activity and expression of the specific NOX subunit NOX4 were significantly increased in APPxPS1 mice in an age-dependent manner, and NOX activity and cognitive impairment shared a significant linear relationship. Data further show that age-dependent increases in Abeta(1-42) had a significant linear relationship with both NOX activity and cognitive performance in APPxPS1 knock-in mice. Collectively, these data show that NOX expression and activity are significantly upregulated with age in this humanized model of Abeta pathogenesis, and suggest that NOX-associated redox pathways are intimately linked to both the loss of cognitive function and the deposition of Abeta(1-42). |
