Affiliations: [a] Department of Neurology, Mount Sinai School of Medicine, New York, NY, USA | [b] Department of Pharmacology, Forest Research Institute, Jersey City, NJ, USA | [c] Department of Bioanalytical and Drug Metabolism, Forest Research Institute, Jersey City, NJ, USA | [d] Geriatric Research, Education and Clinical Center, James J. Peters Veterans Affairs Medical Center, Bronx, NY, USA
Correspondence:
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Correspondence to: Giulio Maria Pasinetti, MD, PhD, Department of Neurology, The Mount Sinai School of Medicine, 1 Gustave L. Levy Place, Box 1137, NY 10029, USA. Tel.: +1 212 241 7938; Fax: +1 212 876 9042; E-mail: [email protected].
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.
