ArticleAnnals of clinical and translational neurology2025
Associations of Cerebrospinal Fluid Orexin-A, Alzheimer Disease Biomarkers, and Cognitive Performance.
Article in Annals of clinical and translational neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Orexin, Sleep, and Cognition in Alzheimer Disease: Non-REM Oscillatory Activity and Neural Resilience.Neurology · 2026Observational
- Wake-promoting neuromodulators in Alzheimer's disease: Implications for sleep and brain clearance.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Signal transduction, dimerization, and therapeutic targeting of Orexin and receptor systems.Frontiers in pharmacology · 2025Review
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Authors and funding
14 authors.
Funding
Abstract
objectiveCerebrospinal fluid (CSF) orexin-A has been suggested to be a biomarker of Alzheimer disease (AD). In both cognitively unimpaired healthy older adults and individuals with symptomatic AD, CSF orexin-A is positively associated with CSF Aβ42, p-tau181, and total tau (t-tau) concentrations. However, a recent systematic review and meta-analysis did not support differences in orexin-A between AD and controls. In this study, we tested the association between CSF orexin-A concentrations, AD biomarkers, and cognitive performance in older adults with and without symptomatic AD.
methodsTwo hundred and seventy community-dwelling older adults underwent standardized cognitive assessments, sleep monitoring with a single-channel electroencephalography test, one night of home sleep apnea testing, biofluid and imaging AD biomarker measurement within 1 year of sleep monitoring, and APOE genotyping. Plasma and CSF AD biomarkers were measured by immunoassay or mass spectrometry. CSF orexin-A was measured by radioimmunoassay.
resultsCSF orexin-A levels did not differ by amyloid positivity, cognitive status, or AD stage. However, CSF AD biomarkers (Aβ40, Aβ42, and t-tau) were positively associated with CSF orexin-A levels even after correction for multiple comparisons. CSF orexin-A was not associated with any measure of cognitive performance.
interpretationThis study showed that CSF orexin-A is associated with multiple CSF AD biomarkers, but not with AD pathology or cognitive performance. We hypothesize that this is due to similar mechanisms of production/release of these proteins with sleep-wake activity. Future studies measuring other forms of orexin peptides, such as orexin-B, may provide evidence for orexin as a marker for AD.
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