Divergent Associations of Slow‐Wave Sleep versus Rapid Eye Movement Sleep with Plasma Amyloid‐Beta

Objective: Recent evidence shows that during slow-wave sleep (SWS), the brain is cleared from potentially toxic metabolites, such as the amyloid-beta protein. Poor sleep or elevated cortisol levels can worsen amyloid-beta clearance, potentially leading to the formation of amyloid plaques, a neuropathological hallmark of Alzheimer disease. Here, we explored how nocturnal neural and endocrine activity affects amyloid-beta fluctuations in the peripheral blood. Methods: We acquired simultaneous polysomnography and all-night blood sampling in 60 healthy volunteers aged 20–68 years. Nocturnal plasma concentrations of amyloid-beta-40, amyloid-beta-42, cortisol, and growth hormone were assessed every 20 minutes. Amyloid-beta fluctuations were modeled with sleep stages, (non)oscillatory power, and hormones as predictors while controlling for age and participant-specific random effects. Results: Amyloid-beta-40 and amyloid-beta-42 levels correlated positively with growth hormone concentrations, SWS proportion, and slow-wave (0.3–4Hz) oscillatory and high-band (30–48Hz) nonoscillatory power, but negatively with cortisol concentrations and rapid eye movement sleep (REM) proportion measured 40–100 minutes previously (all t values > j3j, p values < 0.003). ... mehrOlder participants showed higher amyloid-beta-40 levels. Interpretation: Slow-wave oscillations are associated with higher plasma amyloid-beta levels, whereas REM sleep is related to decreased amyloid-beta plasma levels, possibly representing changes in central amyloid-beta production or clearance. Strong associations between cortisol, growth hormone, and amyloid-beta presumably reflect the sleepregulating role of the corresponding releasing hormones. A positive association between age and amyloid-beta-40
may indicate that peripheral clearance becomes less efficient with age.