Health
Alzheimer’s protein reduced by sleeping pills
Suvorexant (Belsomra), a dual orexin receptor antagonist approved for insomnia, reduced tau phosphorylation and amyloid beta levels. small clinical trial Indicated.
The ratio of phosphorylated tau-threonine-181 (p-tau-181) to non-phosphorylated tau-threonine-181 increased from 10% to 15% in cognitively normal adults treated with suvorexant 20 mg compared with placebo. % decreased, reported Brendan Lucey, MD, MSCI. Washington University School of Medicine, St. Louis, and co-authors.
Amyloid-beta levels were reduced by 10% to 20% compared to placebo starting 5 hours after suvorexant administration, the researchers wrote. Neurological Annals.
“This is a small proof-of-concept study,” Lucy said in a statement. It is not yet known if there is
“Nevertheless, these results are very encouraging,” he added. “This drug is already available and proven to be safe, and there is now evidence that it affects levels of a protein important in the progression of Alzheimer’s disease.”
In recent years, researchers have Complex relationship Between sleep and Alzheimer’s disease.In a previous study, Lucy and his colleagues found that older people with less slow-wave sleep high levels of brain tauOther studies have shown that sleep apnea is associated with higher tau load.
but, which came first the chicken or the egg According to Alzheimer’s researcher Ron Petersen, M.D., Ph.D., of the Mayo Clinic in Rochester, Minnesota, the answer is still unknown. Is the brain disrupting sleep and starting the cycle from there?”
Orexins are neuropeptides that promote wakefulness.Evidence supports a role for the orexin system in the development of Alzheimer’s disease, say Lucey and co-authors. Reduces soluble amyloid beta levels and amyloid plaques.
Lucey et al. enrolled 38 people aged 45 to 65 years without cognitive impairment in a two-night sleep study and treated them with suvorexant 10 mg (n = 13), suvorexant 20 mg (n = 12), or placebo (n = 13). assigned randomly. They assessed cerebrospinal fluid (CSF) via an intrathecal lumbar catheter every 2 hours for 36 hours starting 1 hour before suvorexant or placebo was administered.
Most of the participants were female (68.4%) and Caucasian (78.9%). All were in good health and had no clinical sleep or neurologic disease.
Suvorexant 10 mg had no statistically significant effect on p-tau-181 or amyloid compared to placebo. Neither dose of suvorexant significantly increased total sleep time, sleep efficiency, duration of non-rapid eye movement (REM) sleep, or duration of REM sleep than placebo. Suvorexant did not decrease phosphorylation of tau-serine-202 or tau-threonine-217.
Twenty-four hours after the first dose, p-tau-181 increased, but amyloid levels remained low in the 20 mg group. Administration of 20 mg of suvorexant on the second evening reduced levels of both proteins again.
Suvorexant’s actions may extend beyond night-time sleep induction, Lucy and colleagues observed. They suggested that a mechanistic pathway may be involved, they noted.
“We believe that if we can lower amyloid on a daily basis, the accumulation of amyloid plaques in the brain will decrease over time,” Lucy said. There may be less cell death.”
Findings were limited due to the small sample size of this study. In addition, two of his other dual orexin receptor antagonists, lemborexant (Dayvigo) and daridrexant (Quviviq), recently received FDA approval for the treatment of insomnia. Future studies need to test whether these agents have the same effect on amyloid and tau, he said, Lucey and co-authors.
Disclosure
This study was funded by the National Institutes of Health and the Bright Focus Foundation.
Lucy consulted Merck, which manufactures suvorexant. The co-authors have revealed their relationship with C2N Diagnostics.
Primary information
Neurological Annals
Source reference: Lucey BP, et al. “Suvorexant acutely reduces tau phosphorylation and Aβ in the human CNS.” Ann Neurol 2023; DOI: 10.1002/ana.26641.
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