Increased Cerebrospinal Fluid Amyloid-β During Sleep Deprivation in Healthy Middle-Aged Adults Is Not Due to Stress or Circadian Disruption

Background: Concentrations of soluble amyloid-beta (A beta) oscillate with the sleep-wake cycle in the interstitial fluid of mice and cerebrospinal fluid (CSF) of humans. Further, the concentration of A beta in CSF increases during sleep deprivation. Stress and disruption of the circadian clock are additional mechanisms hypothesized to increase CSF A beta levels. Cortisol is a marker for stress and has an endogenous circadian rhythm. Other factors such as glucose and lactate have been associated with changes in sleep-wake activity and/or A beta. Objective: In this exploratory study, we used samples collected in a previous study to examine how sleep deprivation affects A beta, cortisol, lactate, and glucose in plasma and CSF from healthy middle-aged adults (N = 11). Methods: Eleven cognitively normal participants without evidence of sleep disturbance were randomized to sleep deprivation or normal sleep control. All participants were invited to repeat the study. Cortisol, lactate, glucose, and A beta were measured in 2-h intervals over a 36-h period in both plasma and CSF. All concentrations were normalized to the mean prior to calculating mesor, amplitude, acrophase, and other parameters. Results: One night of sleep deprivation increases the overnight concentration of A beta in CSF approximately 10%, but does not significantly affect cortisol, lactate, or glucose concentrations in plasma or CSF between the sleep-deprived and control conditions. Conclusion: These data suggest that sleep deprivation-related changes in CSF A beta are not mediated by stress or circadian disruption as measured by cortisol.