0224 Sleep Deprivation and Recovery Sleep Impact Serum Biomarkers of Alzheimer's Disease in Retired Adults

Abstract Introduction Short sleep increases Alzheimer’s disease (AD) risk, and sleep facilitates clearance of AD-related metabolites. Blood-based AD biomarkers (e.g., beta amyloid [Aβ] 42/40 ratio, phosphorylated tau181 [p-Tau181], neurofilament light chain [NfL], glial fibrillary acidic protein [GFAP]) are validated and increasingly used clinically. However, the impact of sleep deprivation and recovery sleep on these markers is unclear. This study determined the effects of sleep deprivation and recovery sleep on serum AD biomarkers in retired adults and explored: 1) whether changes in EEG slow-wave activity (SWA) from baseline to recovery sleep were associated with serum AD biomarker changes, and 2) whether findings differed between retired night shift and day workers. Methods Participants were 58 cognitively normal retired shift workers (n = 28) and retired day workers (n = 30). All completed a 60-hour laboratory study including a baseline night of EEG sleep recording, one night of total sleep deprivation, and one night of recovery sleep. EEG SWA (0.5-1Hz) was assessed during baseline and recovery sleep. Blood was collected the morning after each night. Serum samples were analyzed for Aβ40, Aβ42, p-Tau181, NfL, and GFAP using ultra-sensitive immunoassay. Linear mixed models determined the effects of sleep deprivation and recovery sleep on biomarker levels adjusted for age, sex, race/ethnicity, and education. Results Mean participant age was 67.8 +/- 5.5 years, 52% were female, 86% were White, and mean education was 16.0 +/- 1.9 years. Serum Aβ42/40 ratio, NfL, and GFAP decreased following one night of sleep deprivation. Following recovery sleep, the Aβ42/40 ratio remained below baseline, while NfL and GFAP increased to baseline levels. Serum pTau-181 did not change following sleep deprivation or recovery sleep. Greater SWA increase from baseline to recovery sleep was associated with smaller Aβ42/40 ratio decrease. Findings did not differ between shift and day work groups. Conclusion In retired adults, acute sleep deprivation and recovery sleep impacted serum AD biomarker levels. Sleep characteristics may therefore affect the diagnostic accuracy of these tests. Former night shift work exposure did not influence serum biomarker responses, suggesting no effect of long-term shift work exposure over time. SWA may aid Aβ clearance during sleep. Support (if any) K01AG075171, R01AG047139, R01GM140476, R01GM113243