Angiopoietin-1 accelerates Alzheimer's disease via FOXA2/PEN2/APP pathway in APP/PS1 mice

Angiopoietin-1 (Ang-1), a regulatory angiogenesis protein and it has been found to be involved in the occurrence and progression of Alzheimer's disease. However, it was still to be addressed the distinctly role and the molecular mechanisms of Ang-1 affects Alzheimer's disease. Our data suggest that Ang-1 aggravated the accumulation of Aβ₄₂ and cognitive decline in APP/PS1 mice. The upregulation of APPβ is essential for Aβ₄₂ production in N2a cells overexpressing the mutational human APP gene (N2a/APP695 cells), while downregulation of PEN2 could reduce APP expression. Silencing of FOXA2 lead to inhibition of APP expression, as well as decrease of Aβ₄₂ contents. In conclusion, Ang-1 has an accelerative effect on Alzheimer's disease by increasing the secretion of Aβ₄₂ via FOXA2/PEN2/APP pathway.