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 > |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, 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 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. ANN NEUROL 2024;96:46–60 [ABSTRACT FROM AUTHOR]