Divergent associations of slow-wave sleep vs. REM sleep with plasma amyloid-beta

Abstract Background 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’s disease. Here, we explore how nocturnal neural and endocrine activity affects amyloid-beta fluctuations in the peripheral blood as a reflection of cerebral clearance. Methods Simultaneous polysomnography and all-night blood sampling were acquired in 60 healthy volunteers aged 20–68 years old. Nocturnal plasma concentrations of two amyloid-beta species (amyloid-beta-40 and amyloid-beta-42), cortisol, and growth hormone were assessed every 20 minutes from 23:00–7:00. Amyloid-beta fluctuations were modeled with sleep stages, (non)-oscillatory power, and hormones as predictors while controlling for age and multiple comparisons. Time lags between the predictors and amyloid-beta ranged from 20 to 120min. Findings The amyloid-beta-40 and amyloid-beta-42 levels correlated positively with growth hormone concentrations, SWS proportion, slow-wave (0.3–4Hz) oscillatory and high-band (30–48Hz) non-oscillatory power, but negatively with cortisol concentrations and rapid eye movement sleep (REM) proportion measured 40–100min before (all t-values>|3|, p-values<0.003). Older participants showed higher amyloid-beta-40 levels. Interpretation Slow-wave oscillations are associated with higher plasma amyloid-beta levels, reflecting their contribution to cerebral amyloid-beta clearance across the blood-brain barrier. REM sleep is related to decreased amyloid-beta plasma levels; however, this link may reflect passive aftereffects of SWS and not REM’s effects per se. Strong associations between cortisol, growth hormone, and amyloid-beta presumably reflect the sleep-regulating 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. Our study provides important insights into the specificity of different sleep features’ effects on brain clearance and suggests that cortisol nocturnal fluctuations may serve as a new marker of clearance efficiency.