Krüppel-like factor 8 ameliorates Alzheimer's disease by activating β-catenin.

A sustained loss of Wnt signaling function may be involved in the pathology of Alzheimer's disease (AD). Kruppel-like factor 8 (KLF8) induces the activation of Wnt/β-catenin signaling pathway. Thus, KLF8 may be related with the risk of AD. We want to know the role of KLF8 in the development of AD. A rat brain slice model for AD was established. Quantitative RT-PCR, western blotting, and fluorescence staining assays were carried out to examine the effects of KLF8 on the protein expression of some important molecules, which are associated with the development of AD. The enhanced expression level of KLF8 could increase the protein expression level of β-catenin, which interacted with and inhibited nuclear factor-kappa B (NF-κB). The protein levels of KLF8 and β-catenin were increased, while the level of NF-κB was decreased in the AD model. The inhibition of NF-κB was followed by the decrease of the protein expression levels of amyloid precursor protein (APP) and phosphorylated tau (Phospho-Tau). The protein level of KLF8 was decreasing from stages I to IV in patients with AD. This study provides evidence that KLF8 can inhibit the progression of AD.