Valsartan lowers brain β-amyloid protein levels and improves spatial learning in a mouse model of Alzheimer disease

Recent epidemiological evidence suggests that some antihypertensive medications may reduce the risk for Alzheimer disease (AD). We screened 55 clinically prescribed antihypertensive medications for AD-modifying activity using primary cortico-hippocampal neuron cultures generated from the Tg2576 AD m...

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Main Authors: Wang, Jun, Ho, Lap, Chen, Linghong, Zhao, Zhong, Zhao, Wei, Qian, Xianjuan, Humala, Nelson, Seror, Ilana, Bartholomew, Sadie, Rosendorff, Clive, Pasinetti, Giulio Maria
Formato: Artigo
Idioma:Inglês
Publicado em: American Society for Clinical Investigation 2007
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Research Article
Acesso em linha:https://ncbi.nlm.nih.gov/pmc/articles/PMC2040315/
https://ncbi.nlm.nih.gov/pubmed/17965777
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1172/JCI31547
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spelling pubmed-20403152007-11-01 Valsartan lowers brain β-amyloid protein levels and improves spatial learning in a mouse model of Alzheimer disease Wang, Jun Ho, Lap Chen, Linghong Zhao, Zhong Zhao, Wei Qian, Xianjuan Humala, Nelson Seror, Ilana Bartholomew, Sadie Rosendorff, Clive Pasinetti, Giulio Maria J Clin Invest Research Article Recent epidemiological evidence suggests that some antihypertensive medications may reduce the risk for Alzheimer disease (AD). We screened 55 clinically prescribed antihypertensive medications for AD-modifying activity using primary cortico-hippocampal neuron cultures generated from the Tg2576 AD mouse model. These agents represent all drug classes used for hypertension pharmacotherapy. We identified 7 candidate antihypertensive agents that significantly reduced AD-type β-amyloid protein (Aβ) accumulation. Through in vitro studies, we found that only 1 of the candidate drugs, valsartan, was capable of attenuating oligomerization of Aβ peptides into high-molecular-weight (HMW) oligomeric peptides, known to be involved in cognitive deterioration. We found that preventive treatment of Tg2576 mice with valsartan significantly reduced AD-type neuropathology and the content of soluble HMW extracellular oligomeric Aβ peptides in the brain. Most importantly, valsartan administration also attenuated the development of Aβ-mediated cognitive deterioration, even when delivered at a dose about 2-fold lower than that used for hypertension treatment in humans. These preclinical studies suggest that certain antihypertensive drugs may have AD-modifying activity and may protect against progressive Aβ-related memory deficits in subjects with AD or in those at high risk of developing AD. American Society for Clinical Investigation 2007-10-25 2007-11-01 /pmc/articles/PMC2040315/ /pubmed/17965777 http://dx.doi.org/10.1172/JCI31547 Text en Copyright © 2007, American Society for Clinical Investigation
institution US NLM
collection PubMed Central
language Inglês
format Artigo
topic Research Article
spellingShingle Research Article
Wang, Jun
Ho, Lap
Chen, Linghong
Zhao, Zhong
Zhao, Wei
Qian, Xianjuan
Humala, Nelson
Seror, Ilana
Bartholomew, Sadie
Rosendorff, Clive
Pasinetti, Giulio Maria
Valsartan lowers brain β-amyloid protein levels and improves spatial learning in a mouse model of Alzheimer disease
description Recent epidemiological evidence suggests that some antihypertensive medications may reduce the risk for Alzheimer disease (AD). We screened 55 clinically prescribed antihypertensive medications for AD-modifying activity using primary cortico-hippocampal neuron cultures generated from the Tg2576 AD mouse model. These agents represent all drug classes used for hypertension pharmacotherapy. We identified 7 candidate antihypertensive agents that significantly reduced AD-type β-amyloid protein (Aβ) accumulation. Through in vitro studies, we found that only 1 of the candidate drugs, valsartan, was capable of attenuating oligomerization of Aβ peptides into high-molecular-weight (HMW) oligomeric peptides, known to be involved in cognitive deterioration. We found that preventive treatment of Tg2576 mice with valsartan significantly reduced AD-type neuropathology and the content of soluble HMW extracellular oligomeric Aβ peptides in the brain. Most importantly, valsartan administration also attenuated the development of Aβ-mediated cognitive deterioration, even when delivered at a dose about 2-fold lower than that used for hypertension treatment in humans. These preclinical studies suggest that certain antihypertensive drugs may have AD-modifying activity and may protect against progressive Aβ-related memory deficits in subjects with AD or in those at high risk of developing AD.
author Wang, Jun
Ho, Lap
Chen, Linghong
Zhao, Zhong
Zhao, Wei
Qian, Xianjuan
Humala, Nelson
Seror, Ilana
Bartholomew, Sadie
Rosendorff, Clive
Pasinetti, Giulio Maria
author_facet Wang, Jun
Ho, Lap
Chen, Linghong
Zhao, Zhong
Zhao, Wei
Qian, Xianjuan
Humala, Nelson
Seror, Ilana
Bartholomew, Sadie
Rosendorff, Clive
Pasinetti, Giulio Maria
author_sort Wang, Jun
title Valsartan lowers brain β-amyloid protein levels and improves spatial learning in a mouse model of Alzheimer disease
title_short Valsartan lowers brain β-amyloid protein levels and improves spatial learning in a mouse model of Alzheimer disease
title_full Valsartan lowers brain β-amyloid protein levels and improves spatial learning in a mouse model of Alzheimer disease
title_fullStr Valsartan lowers brain β-amyloid protein levels and improves spatial learning in a mouse model of Alzheimer disease
title_full_unstemmed Valsartan lowers brain β-amyloid protein levels and improves spatial learning in a mouse model of Alzheimer disease
title_sort valsartan lowers brain β-amyloid protein levels and improves spatial learning in a mouse model of alzheimer disease
publisher American Society for Clinical Investigation
publishDate 2007
url https://ncbi.nlm.nih.gov/pmc/articles/PMC2040315/
https://ncbi.nlm.nih.gov/pubmed/17965777
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1172/JCI31547
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