Alzheimer's Disease (AD) is the most common cause of dementia. AD patients had increased extracellular amyloid β plaques and intracellular hyperphosphorylated tau (p-tau) in neurons. Recent studies have shown an association between the Renin-Angiotensin System (RAS) and AD. The involvement of RAS has been mediated through Angiotensin II (AngII), which is overexpressed in aging brains. However, the exact mechanism of how AngII contributes to AD is unknown. Thus, we hypothesize that AngII increases p-tau by activating its kinases, CDK5 and MAPK. In the human cortical neuron cell line, HCN2, treatment with AngII upregulated the gene expression of CDK5 (2.9 folds, p < 0.0001) and MAPTK (1.9 folds, p < 0.001). The AT1R antagonist, Losartan, blocked the changes in tau kinases. Also, AngII-induced the MAPK activation, increasing its phosphorylation by 400% (p < 0.0001), an increase that was also blocked by Losartan. An increase in p-tau by AngII was observed using fluorescent microscopy. We then quantified Reactive Oxygen Species (ROS) production, and it was significantly increased by AngII (p < 0.01), and treatment with Losartan blunted their production (p < 0.05). The data obtained demonstrated that AngII might contribute to the pathogenesis of AD.
Keywords: Alzheimer's disease; Angiotensin II; Cortical neurons; Losartan; Reactive oxygen species; Renin-angiotensin-system; Tau phosphorylation.
© 2022 The Authors.