Limits...
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.

Show MeSH

Related in: MedlinePlus

Effect of Aβ -promoting drugs treatment on blood pressure and amyloid neuropathology in Tg2576 mice.(A and D) Measurements of systolic, diastolic blood pressure, and mean arterial blood pressure (MAP) in response to ∼4 weeks of drug treatments. (B and E) Assessment of Aβ1-42 and Aβ1-40 peptide concentrations in the brain of drug treated mice vs. the control mice. (C and F) Assessment of Aβ1-42 and Aβ1-40 in peripheral blood of drug treated mice vs. the control mice. 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


getmorefigures.php?uid=PMC3675203&req=5

pone-0065232-g003: Effect of Aβ -promoting drugs treatment on blood pressure and amyloid neuropathology in Tg2576 mice.(A and D) Measurements of systolic, diastolic blood pressure, and mean arterial blood pressure (MAP) in response to ∼4 weeks of drug treatments. (B and E) Assessment of Aβ1-42 and Aβ1-40 peptide concentrations in the brain of drug treated mice vs. the control mice. (C and F) Assessment of Aβ1-42 and Aβ1-40 in peripheral blood of drug treated mice vs. the control mice. Values represents group mean values (±SEM); n = 3–5 mice per group. **P<0.01, *P<0.05, 2-tailed student t-test.

Mentions: To our surprise, the drugs that increased Aβ in vitro, at the dosage equivalent to human prescription dosage (14.8 mg/kg/day for furosemide and 0.74 mg/kg/day for trandolapril), did not increase total Aβ1-40 or Aβ1-42 in the brain following one-month treatment. On the contrary, both furosemide and trandolapril treatment significantly reduced the levels of total brain amyloid content in the Tg2576 mice following one-months short-term treatment (Figure 3B and 3E) without significantly changing of blood pressure. The reduction of brain Aβ content in both treatments was associated with significant increases of plasma levels of Aβ (Figure 3C and 3F). In parallel studies, we confirmed that the drug treatments did not alter the expression of APP in the brains of the mice using western blot analysis (data not shown).


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 -promoting drugs treatment on blood pressure and amyloid neuropathology in Tg2576 mice.(A and D) Measurements of systolic, diastolic blood pressure, and mean arterial blood pressure (MAP) in response to ∼4 weeks of drug treatments. (B and E) Assessment of Aβ1-42 and Aβ1-40 peptide concentrations in the brain of drug treated mice vs. the control mice. (C and F) Assessment of Aβ1-42 and Aβ1-40 in peripheral blood of drug treated mice vs. the control mice. 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-g003: Effect of Aβ -promoting drugs treatment on blood pressure and amyloid neuropathology in Tg2576 mice.(A and D) Measurements of systolic, diastolic blood pressure, and mean arterial blood pressure (MAP) in response to ∼4 weeks of drug treatments. (B and E) Assessment of Aβ1-42 and Aβ1-40 peptide concentrations in the brain of drug treated mice vs. the control mice. (C and F) Assessment of Aβ1-42 and Aβ1-40 in peripheral blood of drug treated mice vs. the control mice. Values represents group mean values (±SEM); n = 3–5 mice per group. **P<0.01, *P<0.05, 2-tailed student t-test.
Mentions: To our surprise, the drugs that increased Aβ in vitro, at the dosage equivalent to human prescription dosage (14.8 mg/kg/day for furosemide and 0.74 mg/kg/day for trandolapril), did not increase total Aβ1-40 or Aβ1-42 in the brain following one-month treatment. On the contrary, both furosemide and trandolapril treatment significantly reduced the levels of total brain amyloid content in the Tg2576 mice following one-months short-term treatment (Figure 3B and 3E) without significantly changing of blood pressure. The reduction of brain Aβ content in both treatments was associated with significant increases of plasma levels of Aβ (Figure 3C and 3F). In parallel studies, we confirmed that the drug treatments did not alter the expression of APP in the brains of the mice using western blot analysis (data not shown).

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