睡眠薬がアルツハイマーを予防・遅延させるかどうか、さらなる研究が必要 More research needed to determine if sleep medications prevent, delay Alzheimer’s
この研究は、4月20日にAnnals of Neurology誌に掲載されました。
Suvorexantはヒト中枢神経系におけるタウのリン酸化とAβを急性的に低下させる Suvorexant Acutely Decreases Tau Phosphorylation and Aβ in the Human CNS
Brendan P. Lucey, Haiyan Liu , Cristina D. Toedebusch, David Freund,Tiara Redrick, Samir L. Chahin, Kwasi G. Mawuenyega, James G. Bollinger, Vitaliy Ovod, Nicolas R. Barthélemy, Randall J. Bateman
Annals of Neurology Published: 10 March 2023
In Alzheimer’s disease, hyperphosphorylated tau is associated with formation of insoluble paired helical filaments that aggregate as neurofibrillary tau tangles and are associated with neuronal loss and cognitive symptoms. Dual orexin receptor antagonists decrease soluble amyloid-β levels and amyloid plaques in mouse models overexpressing amyloid-β, but have not been reported to affect tau phosphorylation. In this randomized controlled trial, we tested the acute effect of suvorexant, a dual orexin receptor antagonist, on amyloid-β, tau, and phospho-tau.
Thirty-eight cognitively unimpaired participants aged 45 to 65 years were randomized to placebo (N = 13), suvorexant 10 mg (N = 13), and suvorexant 20 mg (N = 12). Six milliliters of cerebrospinal fluid were collected via an indwelling lumbar catheter every 2 hours for 36 hours starting at 20:00. Participants received placebo or suvorexant at 21:00. All samples were processed and measured for multiple forms of amyloid-β, tau, and phospho-tau via immunoprecipitation and liquid chromatography-mass spectrometry.
The ratio of phosphorylated-tau-threonine-181 to unphosphorylated-tau-threonine-181, a measure of phosphorylation at this tau phosphosite, decreased ~10% to 15% in participants treated with suvorexant 20 mg compared to placebo. However, phosphorylation at tau-serine-202 and tau-threonine-217 were not decreased by suvorexant. Suvorexant decreased amyloid-β ~10% to 20% compared to placebo starting 5 hours after drug administration.
In this study, suvorexant acutely decreased tau phosphorylation and amyloid-β concentrations in the central nervous system. Suvorexant is approved by the US Food and Drug Administration to treatment insomnia and may have potential as a repurposed drug for the prevention of Alzheimer’s disease, however, future studies with chronic treatment are needed. ANN NEUROL 2023
Potential Conflicts of Interest
H.L., C.D.T., D.F., T.R., S.L.C., K.G.M., V.O., and J.G.B. had no potential conflicts reported that were relevant to this work. N.R.B. may receive income based on technology (methods of diagnosing AD with phosphorylation changes) licensed by Washington University to C2N Diagnostics (method used for measuring tau phosphorylation). R.J.B. may receive income based on technology (methods of diagnosing AD with phosphorylation changes) licensed by Washington University to C2N Diagnostics (method used for measuring tau phosphorylation). Washington University and R.J.B. have equity ownership interest in C2N Diagnostics and R.J.B. receives income from C2N Diagnostics for serving on the scientific advisory board. B.P.L. has consulted for Merck (maker of suvorexant) in the past 3 years. Merck is also providing suvorexant and matched placebo for a clinical trial funded by a private foundation.