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While disrupted sleep affects canonical AD biomarkers, its impact on other mechanisms, such as circulating microRNAs (miRNAs), remains less understood. Therefore, we here examined the effects of overnight wakefulness on plasma levels of several miRNAs implicated in neurodegeneration and AD, as well as in sleep and circadian regulation\u2014namely miR\u2010127\u20103p, miR\u2010132\u20103p, and miR\u2010142\u20103p. Following a baseline period in each highly controlled in\u2010lab session, in total 15 healthy normal\u2010weight young men underwent two conditions on separate occasions, in randomised order: a night of normal sleep, and a night of sustained wakefulness. After overnight wakefulness, morning plasma levels of miR\u2010127\u20103p and miR\u2010142\u20103p were significantly elevated compared with post\u2010sleep levels. These changes were not associated with the significant increase in self\u2010reported morning stress levels observed after wakefulness compared with sleep. This study is the first to demonstrate that a single night of wakefulness\u2014mimicking overnight shift work\u2014significantly elevates circulating levels of miR\u2010127\u20103p and miR\u2010142\u20103p in humans. These findings, though based on a limited sample size, suggest a potential molecular link between sleep loss and neurodegeneration, warranting further investigation.<\/jats:p>\n                  <jats:p>\n                    <jats:bold>Trial Registration:<\/jats:bold>\n                    Clinical Trial number: NCT01800253;\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.clinicaltrials.gov\">www.clinicaltrials.gov<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1111\/jcmm.70523","type":"journal-article","created":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T23:41:42Z","timestamp":1744069302000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Acute Sleep Loss Increases Circulating Morning Levels of Two MicroRNAs Implicated in Neurodegenerative Disease in Healthy Young 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