title: Central angiotensin II-induced Alzheimer-like tau phosphorylation in normal rat brains.
abstract: Growing evidence suggests that Alzheimer disease (AD) origins in vascular lesions. As the crucial mediator of vascular pathology, angiotensin II-induced significant amyloid production in our laboratory, although amyloid neurotoxicity depended on phosphorylated tau (p-tau) in recent studies. In the present study, p-tau levels were significantly elevated by central angiotensin II via glycogen synthase kinase 3β (GSK 3β) and other tau kinases. Moreover, angiotensin II-induced cognitive impairment and tau phosphorylation was attenuated by losartan and a GSK 3β inhibitor. These findings implicate Ang II as a crucial mediator of AD pathology and a link between cardiovascular events and AD.
authors.affiliation: Department of Neurology, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, PR China.
authors.forename: Minjie
authors.initials: M
authors.lastname: Tian
authors.forename: Donglin
authors.initials: D
authors.lastname: Zhu
authors.forename: Wei
authors.initials: W
authors.lastname: Xie
authors.forename: Jingping
authors.initials: J
authors.lastname: Shi
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D000804:Angiotensin II / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D003071:Cognition / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007211:Indoles / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D008301:Maleimides / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D007211:Indoles; D008301:Maleimides; C417521:SB 216763; D016875:tau Proteins; D000804:Angiotensin II; D011433:Propranolol; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3; D019808:Losartan