| First Author | Zhang W | Year | 2011 |
| Journal | Behav Brain Res | Volume | 222 |
| Issue | 2 | Pages | 342-50 |
| PubMed ID | 21513747 | Mgi Jnum | J:172201 |
| Mgi Id | MGI:5004992 | Doi | 10.1016/j.bbr.2011.03.072 |
| Citation | Zhang W, et al. (2011) Soluble Abeta levels correlate with cognitive deficits in the 12-month-old APPswe/PS1dE9 mouse model of Alzheimer's disease. Behav Brain Res 222(2):342-50 |
| abstractText | Amyloid-beta peptide (Abeta) is believed to be central in the pathogenesis of Alzheimer's disease (AD) characterized by cognitive deficits. However, it remains uncertain which form(s) of Abeta pathology is responsible for the cognitive deficits in AD. In the present study, the cognitive deficits and the profiles of Abeta pathology were characterized in the 12-month-old APPswe/PS1dE9 double transgenic mice, and their correlations were examined. Compared with non-transgenic littermates, the middle-aged APPswe/PS1dE9 mice exhibited spatial learning and memory deficits in the water maze test and long-term contextual memory deficits in the step-down passive avoidance test. Among the middle-aged APPswe/PS1dE9 mice, hippocampal soluble Abeta1-40 and Abeta1-42 levels were highly correlated with spatial learning deficits and long-term contextual memory deficits, as well as cortical and hippocampal soluble Abeta1-40 and Abeta1-42 levels were strongly correlated with spatial memory deficits. By contrast, no significant correlations were observed between three measures of cognitive functions and amyloid plaque burden (total Abeta plaque load and fibrillar Abeta plaque load), total Abeta levels (Abeta1-40 and Abeta1-42), as well as insoluble Abeta levels (Abeta1-40 and Abeta1-42). Stepwise multiple regression analysis identified hippocampal soluble Abeta1-40 and Abeta1-42 levels as independent factors for predicting the spatial learning deficits and the long-term contextual memory deficits, as well as hippocampal and cortical soluble Abeta1-40 and Abeta1-42 levels as independent factors for predicting the spatial memory deficits in transgenic mice. These results demonstrate that cognitive deficits are highly related to the levels of soluble Abeta in middle-aged APPswe/PS1dE9 mice, in which soluble Abeta levels are only a tiny fraction of the amount of total Abeta levels. Consequently, our findings provide further evidence that soluble Abeta might primarily contribute to cognitive deficits in AD, suggesting that reducing the levels of soluble Abeta species would be a therapeutic intervention for AD patients even with large deposits of aggregated, insoluble Abeta. |
