title: Carvedilol as a potential novel agent for the treatment of Alzheimer's disease.
abstract: Oligomeric β-amyloid (Aβ) has recently been linked to synaptic plasticity deficits, which play a major role in progressive cognitive decline in Alzheimer's disease (AD). Here we present evidence that chronic oral administration of carvedilol, a nonselective β-adrenergic receptor blocker, significantly attenuates brain oligomeric β-amyloid content and cognitive deterioration in 2 independent AD mouse models. We found that carvedilol treatment significantly improved neuronal transmission, and that this improvement was associated with the maintenance of number of the less stable "learning" thin spines in the brains of AD mice. Our novel observation that carvedilol interferes with the neuropathologic, biochemical, and electrophysiological mechanisms underlying cognitive deterioration in AD supports the potential development of carvedilol as a treatment for AD.
authors.affiliation: Department of Neurology, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Ono
authors.forename: Dara L
authors.initials: DL
authors.lastname: Dickstein
authors.forename: Isabel
authors.initials: I
authors.lastname: Arrieta-Cruz
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.forename: Xianjuan
authors.initials: X
authors.lastname: Qian
authors.forename: Ashley
authors.initials: A
authors.lastname: Lamparello
authors.forename: Rakesh
authors.initials: R
authors.lastname: Subnani
authors.forename: Mario
authors.initials: M
authors.lastname: Ferruzzi
authors.forename: Constantine
authors.initials: C
authors.lastname: Pavlides
authors.forename: Lap
authors.initials: L
authors.lastname: Ho
authors.forename: Patrick R
authors.initials: PR
authors.lastname: Hof
authors.forename: David B
authors.initials: DB
authors.lastname: Teplow
authors.forename: Giulio M
authors.initials: GM
authors.lastname: Pasinetti
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002227:Carbazoles / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use*; D000077261:Carvedilol; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D011412:Propanolamines / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol