The VEGF inhibitor vatalanib regulates AD pathology in 5xFAD mice

Abstract

Alzheimer's disease (AD) is a highly prevalent neurodegenerative disease characterized by A beta accumulation and tau hyperphosphorylation. Epidemiological evidence for a negative correlation between cancer and AD has led to the proposed use of tyrosine kinase inhibitors (TKIs) such as dasatinib and masitinib for AD, with reported beneficial effects in the AD brain. The TKI vatalanib inhibits angiogenesis by inhibiting vascular endothelial growth factor receptor (VEGFR). Although changes in VEGF and VEGFR have been documented in AD, the effect of vatalanib on AD pathology has not been investigated. In this study, the effects of vatalanib on tau phosphorylation and A beta accumulation in 5xFAD mice, a model of AD, were evaluated by immunohistochemistry. Vatalanib administration significantly reduced tau phosphorylation at AT8 and AT100 by increasing p-GSK-3 beta (Ser9) in 5xFAD mice. In addition, vatalanib reduced the number and area of A beta plaques in the cortex in 5xFAD mice. Our results suggest that vatalanib has potential as a regulator of AD pathology.