Carvedilol as a potential novel agent for the treatment of Alzheimer's disease.
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.
Wang
Jun
J
Department of Neurology, Mount Sinai School of Medicine, New York, NY 10029, USA.
Ono
Kenjiro
K
Dickstein
Dara L
DL
Arrieta-Cruz
Isabel
I
Zhao
Wei
W
Qian
Xianjuan
X
Lamparello
Ashley
A
Subnani
Rakesh
R
Ferruzzi
Mario
M
Pavlides
Constantine
C
Ho
Lap
L
Hof
Patrick R
PR
Teplow
David B
DB
Pasinetti
Giulio M
GM
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
D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol