Effects of acute sleep deprivation on individuals across different APOE genotypes: a randomized controlled trial protocol

Background

Sleep is crucial for the clearance of metabolic waste products. Sleep deprivation leads to the accumulation of amyloid-β (Aβ) and tau proteins, which may be mediated by impaired glymphatic clearance, thereby contributing to the hallmark pathologies of Alzheimer's disease (AD). The apolipoprotein E (APOE) gene, particularly the APOE ε4 allele, is a major genetic risk factor for AD and is also closely associated with sleep. Notably, the interaction between poor sleep and APOE ε4 may further enhance AD risk. However, prior studies have reported inconsistent effects of sleep deprivation on AD related biomarkers, and clinical studies stratified by APOE genotype are lacking. This study aims to investigate the effects of 24-h acute sleep deprivation on plasma AD biomarkers and to assess APOE genotype-dependent responses.