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 (Abeta) oscillate with the sleep-wake cycle in the interstitial fluid of mice and cerebrospinal fluid (CSF) of humans. Further, the concentration of Abeta in CSF increases during sleep deprivation. Stress and disruption of the circadian clock are additional mechanisms hypothesized to increase CSF Abeta levels. Cortisol is a marker for both 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 Abeta. OBJECTIVE: In this exploratory study, we used samples collected in a previous study to examine how sleep deprivation affects Abeta, 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 Abeta 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 Abeta 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 Abeta are not mediated by stress or circadian disruption as measured by cortisol.