{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T14:07:24Z","timestamp":1790086044466,"version":"4.0.1"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"\n Background<\/jats:title>\n \n Sleep is crucial for the clearance of metabolic waste products. Sleep deprivation leads to the accumulation of amyloid-\n \u03b2<\/jats:italic>\n (A\u03b2) and tau proteins, which may be mediated by impaired glymphatic clearance, thereby contributing to the hallmark pathologies of Alzheimer\u2019s disease (AD). The apolipoprotein E (APOE) gene, particularly the\n APOE<\/jats:italic>\n \u03b54 allele, is a major genetic risk factor for AD and is also closely associated with sleep. Notably, the interaction between poor sleep and APOE \u03b54 may further enhance AD risk. However, prior studies have reported inconsistent effects of sleep deprivation on AD related biomarkers, and clinical studies stratified by\n APOE<\/jats:italic>\n genotype are lacking. This study aims to investigate the effects of 24-h acute sleep deprivation on plasma AD biomarkers and to assess\n APOE<\/jats:italic>\n genotype-dependent responses.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n This prospective, randomized open-label, blinded-endpoint trial plans to enroll 60 healthy young adults. Participants will be stratified by\n APOE<\/jats:italic>\n genotype into three groups at a 1:1:1 ratio:\n APOE<\/jats:italic>\n \u03b53\/\u03b53 homozygotes,\n APOE<\/jats:italic>\n \u03b54 carriers (\u03b53\/\u03b54 and \u03b54\/\u03b54 genotypes), and\n APOE<\/jats:italic>\n \u03b52 carriers (\u03b52\/\u03b53 and \u03b52\/\u03b52 genotypes). Within each genotype stratum, participants will be randomly assigned in a 1:1 ratio to either the 24-h acute sleep deprivation group or the normal sleep group. The primary outcome is the change in plasma A\u03b2\n 42<\/jats:sub>\n levels from baseline to day 1 after randomization. Secondary outcomes include changes from baseline to day 1 after randomization in plasma levels of the following biomarkers: A\u03b2\n 40<\/jats:sub>\n , total tau (t-tau), phosphorylated tau-181 (p-tau181), phosphorylated tau-217 (p-tau217), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP). Additionally, the following ratios will be assessed: A\u03b2\n 42<\/jats:sub>\n \/A\u03b2\n 40<\/jats:sub>\n , t-tau\/A\u03b2\n 42<\/jats:sub>\n , p-tau181\/A\u03b2\n 42<\/jats:sub>\n , and p-tau217\/A\u03b2\n 42<\/jats:sub>\n . Changes in neuropsychiatric and cognitive assessment will also be evaluated, including scores on the Fatigue Scale-14 (FS-14), the Positive and Negative Affect Schedule (PANAS), and performance on the N-back tasks. Exploratory outcomes include changes in plasma proteomics and metabolomics, as well as positron emission tomography\/magnetic resonance imaging (PET\/MRI) measures.\n <\/jats:p>\n <\/jats:sec>\n \n Discussion<\/jats:title>\n \n This study serves as the first randomized controlled trial (RCT) to explore the potential influence of acute sleep deprivation on plasma AD biomarkers across different\n APOE<\/jats:italic>\n genotypes, with the largest sample size among current RCTs on sleep deprivation. This trial is expected to generate critical evidence elucidating the impact of 24-h acute sleep deprivation on the pathophysiology of AD and to inform the development of future sleep-focused preventive interventions.\n <\/jats:p>\n <\/jats:sec>\n \n Study protocol registration<\/jats:title>\n \n ClinicalTrials.gov<\/jats:uri>\n , identifier NCT07085754.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fneur.2026.1805467","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T13:52:37Z","timestamp":1790085157000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of acute sleep deprivation on individuals across different APOE genotypes: a randomized controlled trial protocol"],"prefix":"10.3389","volume":"17","author":[{"given":"He-Jin","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Neurology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine","place":["Guangzhou, Guangdong, China"]},{"name":"Department of Neurology, Guangdong Provincial Hospital of Chinese Medicine","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling-Ling","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine","place":["Guangzhou, Guangdong, China"]},{"name":"Department of Neurology, Guangdong Provincial Hospital of Chinese Medicine","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Hang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine","place":["Guangzhou, Guangdong, China"]},{"name":"Department of Neurology, Guangdong Provincial Hospital of Chinese Medicine","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Hui","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine","place":["Guangzhou, Guangdong, China"]},{"name":"Department of Neurology, Guangdong Provincial Hospital of Chinese Medicine","place":["Guangzhou, Guangdong, China"]},{"name":"State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Neurology, Beijing Tiantan Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye-Feng","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine","place":["Guangzhou, Guangdong, China"]},{"name":"Department of Neurology, Guangdong Provincial Hospital of Chinese Medicine","place":["Guangzhou, Guangdong, China"]},{"name":"State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi-Jie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine","place":["Guangzhou, Guangdong, China"]},{"name":"Department of Neurology, Guangdong Provincial Hospital of Chinese Medicine","place":["Guangzhou, Guangdong, China"]},{"name":"State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine","place":["Guangzhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"e2504961122","DOI":"10.1073\/pnas.2504961122","article-title":"Neurofluid circulation changes during a focused attention style of mindfulness meditation","volume":"122","author":"Keating","year":"2025","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"e28819","DOI":"10.1016\/j.heliyon.2024.e28819","article-title":"Sleep deprivation: a risk factor for the pathogenesis and progression of Alzheimer's disease","volume":"10","author":"Han","year":"2024","journal-title":"Heliyon"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1126\/science.1241224","article-title":"Sleep drives metabolite clearance from the adult 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