Trial reportAnnals of neurology2023
Suvorexant Acutely Decreases Tau Phosphorylation and Aβ in the Human CNS.
Trial report in Annals of neurology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
63 citing papers in PubMed, 1 synthesis or guideline pooled it, 85 citations in OpenAlex.
- Sleep disorders in Parkinson's disease: evaluating pharmacological treatments through systematic review and meta-analysis.BMC neurology · 2025Pooled it
- A Randomized-Controlled Trial Targeting Cognition in Early Alzheimer's Disease by Improving Sleep with Trazodone (REST).Journal of Alzheimer's disease : JAD · 2024Trial
- The glymphatic-lymphatic axis: known pathways, open questions, and emerging roles in neurodegeneration.Translational neurodegeneration · 2026Review
- Association Between Alzheimer Pathology, Sleep, and Cognition in Patients With Late-Onset Unexplained Epilepsy.Neurology · 2026Article
- Integrative role of orexigenic peptides in neuroprotection and neurodegenerative disease modulation.Bioscience reports · 2026Review
- Stress, stress systems, and Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Dual orexin receptor antagonism with lemborexant enhances microglial clearance of β-amyloid in mice.Molecular neurodegeneration · 2026Article
- Sleep-Dependent Clearance of Brain Metabolites via the Glymphatic System: Implications for Alzheimer's Pathophysiology.Brain and behavior · 2026Review
- The spleen-brain axis in Alzheimer's disease and related dementias: Integrating immune and metabolic regulation.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Wake-promoting neuromodulators in Alzheimer's disease: Implications for sleep and brain clearance.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- The Neuropsychiatric Disturbances of Delirium: A Review of Syndromes and Their Treatment.The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry · 2026Review
- Longitudinal association between sleep and Alzheimer's pathology.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Systems biology of Alzheimer's Disease: a scoping review of key pathways and mechanisms.Molecular neurodegeneration · 2026Article
- Sleep disturbances and Alzheimer's disease: a multiscale approach from exposome to neurobiology and precision medicine.GeroScience · 2026Review
- Transplantation of GABAergic Interneuron Progenitors Restores Cortical Circuit Function in an Alzheimer's Disease Mouse Model.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Activation of LH orexin neurons and VTA dopamine neurons is involved in anesthesia/surgery-induced sleep-wake disorders and delirium-like behaviors in mice.Scientific reports · 2026Article
- Beyond traditional sleeping pills: safety, efficacy and multidisease potential of three approved orexin receptor antagonists.Frontiers in psychiatry · 2026Review
- Unraveling Neurodegenerative Disorders: The Potential of Indole and Imidazole-Based Heterocycles.Current topics in medicinal chemistry · 2026Review
- The orexin system as a pharmacological target in inflammation: peripheral mechanisms and safety implications.Frontiers in pharmacology · 2026Review
- Mass Spectrometry-Based Quantification of Orexin Species in Human Cerebrospinal Fluid Reveals Differential Dynamics Associated with Sleep.medRxiv : the preprint server for health sciences · 2025Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveIn 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.
methodsThirty-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.
resultsThe 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.
interpretationIn 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;94:27-40.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.