Affiliations: [a] Department of Pathophysiology, Key Laboratory of Neurological Disease of National Education Ministry, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China | [b] Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China | [c] Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA
Correspondence:
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Correspondence to: Xiao-Chuan Wang, Department of Pathophysiology, Key Laboratory of Neurological Disease of National Education Ministry, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. E-mail: wxch@mails.tjmu.edu.cn.
Note: [1] These authors contributed equally to this work.
Abstract: Recent studies have reported a correlation between dementia and low blood pressure. How hypotension is associated with the increased risk of Alzheimer's disease (AD) remains unclear. Here we show that one month treatment of losartan, an angiotensin II type 1 (AT1) receptor antagonist, causes chronic and sustained hypotension, along with oxidative stress in adult male Sprague-Dawley rats. Furthermore, we show that losartan treatment increases the level of inactivated protein phosphatase 2A (PP2A) and the hyperphosphorylation of tau at Ser 199 and Ser 396. Rats treated with losartan present memory deficits and decreases in spine-density. These findings suggest that losartan-induced hypotension may increase the risk of AD-like pathological alteration and behavioral impairment through oxidative stress which leads to tau hyperphosphorylation and loss of dendritic spines.
