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Unintended effects of cardiovascular drugs on the pathogenesis of Alzheimer's disease.

Wang J, Zhao Z, Lin E, Zhao W, Qian X, Freire D, Bilski AE, Cheng A, Vempati P, Ho L, Ono K, Yamada M, Pasinetti GM - PLoS ONE (2013)

Bottom Line: Among these medications, some might benefit, while others might exacerbate, the pathogenesis of AD.Our study suggests that some commonly prescribed drugs might exert unintended effects and modulate AD and provides the basis for continuing investigation of the role of individual drugs on a case-by-case basis.This line of investigation will lead to the identification of common medications that are potentially beneficial or detrimental to AD as a reference for physicians to consider when prescribing the most appropriate drugs for their patients, particularly for treating chronic disorders among the growing geriatric population.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Mount Sinai School of Medicine, New York, New York, United States of America.

ABSTRACT
Alzheimer's disease (AD) is rapidly becoming one of the leading causes of disability and mortality in the elderly. As life-expectancy increases, an increasing number of people will rely on modern medicines to treat age-associated disorders. Among these medications, some might benefit, while others might exacerbate, the pathogenesis of AD. We screened 1,600 FDA approved drugs for β-amyloid (Aβ)-modifying activity and identified drugs that can potentially influence amyloid precursor protein processing. In this study, we focused on cardiovascular drugs and demonstrated that some hypertensive medication can differentially modulate Aβ, both in vitro and in vivo. Our study suggests that some commonly prescribed drugs might exert unintended effects and modulate AD and provides the basis for continuing investigation of the role of individual drugs on a case-by-case basis. This line of investigation will lead to the identification of common medications that are potentially beneficial or detrimental to AD as a reference for physicians to consider when prescribing the most appropriate drugs for their patients, particularly for treating chronic disorders among the growing geriatric population.

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Related in: MedlinePlus

Effect of Aβ-lowering drug treatment on blood pressure and amyloid neuropathology in Tg2576 mice.(A–F) Measurements of systolic, diastolic blood pressure, and mean arterial blood pressure (MAP) and heart beat (pulse) in response to ∼4 weeks of drug treatments. (G-L) Assessment of Aβ1-42 and Aβ1-40 peptide concentrations in the brain of drug treated mice vs. the control mice. (M-R) Assessment of Aβ1-42 and Aβ1-40 in peripheral blood of drug treated mice vs. the control mice. Blood pressure determination for each animal was calculated as the mean of 10 individual measurements. Values represents group mean values (+SEM); n = 3–5 mice per group. **P<0.01, *P<0.05, 2-tailed student t-test.
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pone-0065232-g002: Effect of Aβ-lowering drug treatment on blood pressure and amyloid neuropathology in Tg2576 mice.(A–F) Measurements of systolic, diastolic blood pressure, and mean arterial blood pressure (MAP) and heart beat (pulse) in response to ∼4 weeks of drug treatments. (G-L) Assessment of Aβ1-42 and Aβ1-40 peptide concentrations in the brain of drug treated mice vs. the control mice. (M-R) Assessment of Aβ1-42 and Aβ1-40 in peripheral blood of drug treated mice vs. the control mice. Blood pressure determination for each animal was calculated as the mean of 10 individual measurements. Values represents group mean values (+SEM); n = 3–5 mice per group. **P<0.01, *P<0.05, 2-tailed student t-test.

Mentions: We found that short-term drug treatment for one month in Tg2576 mice, delivered in the drinking water at clinical dosage, did not significantly influence animal body weight, except for hydralazine treatment (Table 3), which showed a significant body weight drop following 1 month treatment. However, propranolol and losartan treatment resulted in a significantly influenced blood pressure, ∼20% drop in systolic, diastolic and mean arterial pressure (MAP) measurements was observed, while other drugs showed no effect on the blood pressure measurements in the normotensive mice (Figure 2, A-F). The lack of hypotensive effect of the other drugs can be due to: 1) some of the drugs, such as nicardipine, significantly reduce the blood pressure in hypertensive subjects, but have minimal effect on blood pressure in normotensive subjects. 2) the drug dose conversion between species we used in the study is based on the body surface area. It is possible that the absorption and metabolism of certain drug might be different in mice compared to humans.


Unintended effects of cardiovascular drugs on the pathogenesis of Alzheimer's disease.

Wang J, Zhao Z, Lin E, Zhao W, Qian X, Freire D, Bilski AE, Cheng A, Vempati P, Ho L, Ono K, Yamada M, Pasinetti GM - PLoS ONE (2013)

Effect of Aβ-lowering drug treatment on blood pressure and amyloid neuropathology in Tg2576 mice.(A–F) Measurements of systolic, diastolic blood pressure, and mean arterial blood pressure (MAP) and heart beat (pulse) in response to ∼4 weeks of drug treatments. (G-L) Assessment of Aβ1-42 and Aβ1-40 peptide concentrations in the brain of drug treated mice vs. the control mice. (M-R) Assessment of Aβ1-42 and Aβ1-40 in peripheral blood of drug treated mice vs. the control mice. Blood pressure determination for each animal was calculated as the mean of 10 individual measurements. Values represents group mean values (+SEM); n = 3–5 mice per group. **P<0.01, *P<0.05, 2-tailed student t-test.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3675203&req=5

pone-0065232-g002: Effect of Aβ-lowering drug treatment on blood pressure and amyloid neuropathology in Tg2576 mice.(A–F) Measurements of systolic, diastolic blood pressure, and mean arterial blood pressure (MAP) and heart beat (pulse) in response to ∼4 weeks of drug treatments. (G-L) Assessment of Aβ1-42 and Aβ1-40 peptide concentrations in the brain of drug treated mice vs. the control mice. (M-R) Assessment of Aβ1-42 and Aβ1-40 in peripheral blood of drug treated mice vs. the control mice. Blood pressure determination for each animal was calculated as the mean of 10 individual measurements. Values represents group mean values (+SEM); n = 3–5 mice per group. **P<0.01, *P<0.05, 2-tailed student t-test.
Mentions: We found that short-term drug treatment for one month in Tg2576 mice, delivered in the drinking water at clinical dosage, did not significantly influence animal body weight, except for hydralazine treatment (Table 3), which showed a significant body weight drop following 1 month treatment. However, propranolol and losartan treatment resulted in a significantly influenced blood pressure, ∼20% drop in systolic, diastolic and mean arterial pressure (MAP) measurements was observed, while other drugs showed no effect on the blood pressure measurements in the normotensive mice (Figure 2, A-F). The lack of hypotensive effect of the other drugs can be due to: 1) some of the drugs, such as nicardipine, significantly reduce the blood pressure in hypertensive subjects, but have minimal effect on blood pressure in normotensive subjects. 2) the drug dose conversion between species we used in the study is based on the body surface area. It is possible that the absorption and metabolism of certain drug might be different in mice compared to humans.

Bottom Line: Among these medications, some might benefit, while others might exacerbate, the pathogenesis of AD.Our study suggests that some commonly prescribed drugs might exert unintended effects and modulate AD and provides the basis for continuing investigation of the role of individual drugs on a case-by-case basis.This line of investigation will lead to the identification of common medications that are potentially beneficial or detrimental to AD as a reference for physicians to consider when prescribing the most appropriate drugs for their patients, particularly for treating chronic disorders among the growing geriatric population.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Mount Sinai School of Medicine, New York, New York, United States of America.

ABSTRACT
Alzheimer's disease (AD) is rapidly becoming one of the leading causes of disability and mortality in the elderly. As life-expectancy increases, an increasing number of people will rely on modern medicines to treat age-associated disorders. Among these medications, some might benefit, while others might exacerbate, the pathogenesis of AD. We screened 1,600 FDA approved drugs for β-amyloid (Aβ)-modifying activity and identified drugs that can potentially influence amyloid precursor protein processing. In this study, we focused on cardiovascular drugs and demonstrated that some hypertensive medication can differentially modulate Aβ, both in vitro and in vivo. Our study suggests that some commonly prescribed drugs might exert unintended effects and modulate AD and provides the basis for continuing investigation of the role of individual drugs on a case-by-case basis. This line of investigation will lead to the identification of common medications that are potentially beneficial or detrimental to AD as a reference for physicians to consider when prescribing the most appropriate drugs for their patients, particularly for treating chronic disorders among the growing geriatric population.

Show MeSH
Related in: MedlinePlus