Periodic Variation of AAK1 in an Aβ1-42-Induced Mouse Model of Alzheimer's Disease.

Inhibition of endocytosis in an Alzheimer's disease (AD) model has been shown to be able to prevent amyloid β (Aβ)-induced damage and to exert a beneficial effect in treating AD. Adaptor-associated kinase 1 (AAK1), which binds to the adaptor protein complex 2 (AP-2), regulates the process of clathrin-mediated endocytosis. However, how AAK1 expression varies over the course of AD is unknown. In this study, we investigated AAK1 levels in AD model mice over time. Aβ1-42 was used to establish a mouse AD model, and the Morris water maze test was used to characterize the time course of Aβ1-42-induced cognition changes. ELISA was used to determine AAK1 levels in plasma and Aβ1-42 levels in brain tissues. Subsequently, the protein or gene levels of AAK1, AP-2, and Rab5 (an early endosome marker) were tested in each group. The cognitive function of Aβ1-42-induced mice was significantly declined compared to control group, and the deficits reached a peak on day 14, but partly recovered on day 30. Moreover, the level of Aβ1-42 detected with ELISA was highest on day 14, but reduced on day 30, paralleling the cognitive changes in the mice in our study. AAK1, AP-2, and Rab5 expression showed the same periodic variation as the changes in cognition. Thus, periodic variation in AAK1 expression is closely correlated to the decline in cognition, and AAK1 might be a suitable indicator for Alzheimer's disease.