title: Unintended effects of cardiovascular drugs on the pathogenesis of Alzheimer's disease.
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.
authors.affiliation: Department of Neurology, Mount Sinai School of Medicine, New York, New York, United States of America.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Zhong
authors.initials: Z
authors.lastname: Zhao
authors.forename: Emi
authors.initials: E
authors.lastname: Lin
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.forename: Xianjuan
authors.initials: X
authors.lastname: Qian
authors.forename: Daniel
authors.initials: D
authors.lastname: Freire
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Bilski
authors.forename: Alice
authors.initials: A
authors.lastname: Cheng
authors.forename: Prashant
authors.initials: P
authors.lastname: Vempati
authors.forename: Lap
authors.initials: L
authors.lastname: Ho
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Ono
authors.forename: Masahito
authors.initials: M
authors.lastname: Yamada
authors.forename: Giulio M
authors.initials: GM
authors.lastname: Pasinetti
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000819:agonists* / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D002317:Cardiovascular Agents / Q000009:adverse effects*; D004195:Disease Models, Animal; D004622:Embryo, Mammalian; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D061251:Primary Cell Culture
chemical_list: D016564:Amyloid beta-Protein Precursor; D002317:Cardiovascular Agents