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.
Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alzheimer Disease / metabolism*
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Alzheimer Disease / pathology
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Alzheimer Disease / physiopathology
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Angiotensin II / administration & dosage
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Angiotensin II / metabolism
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Angiotensin II / pharmacology*
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Animals
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Brain / drug effects*
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Brain / metabolism*
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Brain / pathology
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Brain / physiopathology
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Cognition / drug effects
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Dose-Response Relationship, Drug
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Enzyme Activation / drug effects
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Glycogen Synthase Kinase 3 / metabolism
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Glycogen Synthase Kinase 3 beta
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Hippocampus / drug effects
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Hippocampus / metabolism
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Hippocampus / pathology
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Hippocampus / physiopathology
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Indoles / pharmacology
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Losartan / pharmacology
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Male
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Maleimides / pharmacology
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Phosphorylation / drug effects
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Propranolol / pharmacology
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Rats
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Rats, Sprague-Dawley
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Signal Transduction / drug effects
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tau Proteins / metabolism*
Substances
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Indoles
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Maleimides
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SB 216763
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tau Proteins
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Angiotensin II
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Propranolol
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Glycogen Synthase Kinase 3 beta
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Gsk3b protein, rat
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Glycogen Synthase Kinase 3
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Losartan