Carvedilol as a potential novel agent for the treatment of Alzheimer's disease

NEUROBIOLOGY OF AGING

卷:32

Article

Wang, Jun^1,2  Ono, Kenjiro^3,4  Dickstein, Dara L.⁵  Arrieta-Cruz, Isabel¹  Zhao, Wei¹  Qian, Xianjuan¹  Lamparello, Ashley¹  Subnani, Rakesh¹  Ferruzzi, Mario⁶  Pavlides, Constantine⁷  Ho, Lap^1,2,8  Hof, Patrick R.⁵  Teplow, David B.^3,4  Pasinetti, Giulio M.^1,2,5,8 

[1] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA

[2] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA

[3] Univ Calif Los Angeles, Brain Res Inst, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90024 USA

[4] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90024 USA

[5] Mt Sinai Sch Med, Dept Neurosci, New York, NY 10029 USA

[6] Purdue Univ, Dept Food Sci, W Lafayette, IN 47907 USA

[7] Rockefeller Univ, New York, NY 10021 USA

[8] James J Peters Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA

关键词: Oligomeric A beta;    Cognitive function;    Spatial memory;    Basal neuronal transmission;    Dendritic spine;    Synaptic plasticity;    Bioavailability;   

DOI  :  10.1016/j.neurobiolaging.2010.05.004

来源: Elsevier

【 摘 要 】

Oligomeric beta-amyloid (A beta) 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 beta-adrenergic receptor blocker, significantly attenuates brain oligomeric beta-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. (C) 2011 Elsevier Inc. All rights reserved.

【 授权许可】

Free