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.
KeywordsAβ1–42 AAK1 Alzheimer’s disease Cognition Endocytosis
Adaptor-associated kinase 1
Analysis of variance
β-amyloid precursor protein
Adaptor protein complex 2
β-site APP cleaving enzyme
Enzyme-linked immunosorbent assay
Morris water maze
Phosphate buffer solution
Real-time polymerase chain reaction
Tris-buffered saline and Tween
This study was supported by grants from, the Key Project of Chongqing Municipal Health Bureau (2016ZDXM005), the Sub-project of National Science and Technology Supporting Program of the Ministry of Science and Technology of China (2015BAI06B04), the National Key Clinical Specialties Construction Program of China (No. 544), grants from the Key Project of Social Undertakings and People’s Livelihood Security of Chongqing Science and Technology Commission (cstc2017shms-zdyfX0009), the Sub-project under the Science and Technology Benefit Plan of Chongqing Science and Technology Commission (cstc2015jcsf10001–01-01), and the Postgraduate Research Innovation Project of Chongqing (CYS16122).
Compliance with Ethical Standards
Conflicts of Interest
The authors declare that they have no conflict of interest.
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