title: Investigation of nebivolol as a novel therapeutic agent for the treatment of Alzheimer's disease.
abstract: Nebivolol is a selective β1 adrenergic receptor antagonist with nitric oxide-mediated vasodilatory properties utilized in the treatment of hypertension. Previously, nebivolol was shown to modulate amyloid-β protein precursor processing in vitro. In this study, we investigated the in vivo effects of nebivolol on the modulation of amyloid neuropathology in the Tg2576 mouse model of Alzheimer's disease (AD). We found that nebivolol is brain bioavailable and can be readily detected in the brain following three weeks of treatment at a dose of 1 mg/kg/day. Moreover, this treatment regime resulted in a significant reduction of amyloid-β neuropathology in the brain, and this reduction was inversely correlated with plasma levels of amyloid-β. Chronic nebivolol treatment of Tg2576 mice with established amyloid neuropathology and cognitive impairments significantly reduced brain amyloid content but failed to improve cognitive function. Our study demonstrates that nebivolol is highly tolerable and safe and can significantly reduce amyloid neuropathology in the brain, which could be one of the most important parameters for primary prevention of AD. Our studies support the continued investigation of nebivolol for the treatment of AD at very early stages of the disease.
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: Harold M
authors.initials: HM
authors.lastname: Wright
authors.forename: Prashant
authors.initials: P
authors.lastname: Vempati
authors.forename: Henry
authors.initials: H
authors.lastname: Li
authors.forename: Julie
authors.initials: J
authors.lastname: Wangsa
authors.forename: Anastasiya
authors.initials: A
authors.lastname: Dzhuan
authors.forename: Karishma
authors.initials: K
authors.lastname: Habbu
authors.forename: Lindsay A
authors.initials: LA
authors.lastname: Knable
authors.forename: Lap
authors.initials: L
authors.lastname: Ho
authors.forename: Giulio M
authors.initials: GM
authors.lastname: Pasinetti
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000378:metabolism / Q000627:therapeutic use*; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001578:Benzopyrans / Q000378:metabolism / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004983:Ethanolamines / Q000378:metabolism / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D000068577:Nebivolol; D016896:Treatment Outcome
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D001578:Benzopyrans; D004983:Ethanolamines; D000068577:Nebivolol