This study aims to investigate the effects of 24-hour acute sleep deprivation on plasma Alzheimer's disease biomarkers and multi-omics in individuals with different APOE genotypes, to elucidate the potential role of acute sleep deprivation in AD risk.

This is a randomized controlled trial designed to enroll 60 healthy volunteers. Stratified randomization will be used, with three strata defined by APOE genotype (APOE ε3/3, APOE ε4 carriers, and APOE ε2 carriers) in a 1:1:1 ratio. Within each stratum, participants will be randomly assigned in a 1:1 ratio to either the acute sleep-deprivation group or the non-acute sleep-deprivation group. The intervention will consist of 24 hours of acute sleep deprivation. The primary outcome measure is the change from baseline in plasma Aβ42 on the first day after randomization.

Inclusion Criteria:

• Age 18-40 years, gender not limited
• Healthy (with no clinically significant abnormal findings in the physical examination report or self-reporting as healthy) and not on medications
• Cognitively normal (Mini-Mental State Examination (MMSE) score > 28)
• Sleep duration of 7-9 hours per night, good sleep quality (Pittsburgh Sleep Quality Index (PSQI) ≤ 5 points)
• Written informed consent, voluntarily participate in this study, and be able to cooperate with the physician to complete the clinical study

Exclusion Criteria:

• Presence of day-night sleep reversal
• Shift work within the past 6 months
• Travel across time zones or experience of jet lag within the past three weeks
• Current smoking or nicotine use; alcohol consumption exceeding five standard units per week (one standard alcohol unit is defined as 10 mL [or 8 g] of pure alcohol)
• Consumption of strong tea, coffee, or caffeine-containing foods and beverages within one week before study participation
• Family history of early-onset dementia
• Self-Rating Depression Scale (SDS) score ≥ 53, Self-Rating Anxiety Scale (SAS) score ≥ 50
• Female participants who are currently pregnant or breastfeeding
• Individuals who need to drive or operate vehicles or machinery during the study period