Sleep deprivation and organic effects in the central nervous system Dynamics of biomarkers in cerebrospinal fluid

Abstract

Degree Project Thesis, Programme in Medicine. TITLE: Sleep deprivation and organic effects in the central nervous system Dynamics of biomarkers in cerebrospinal fluid. Objectives This study addresses potential CSF and blood biomarkers that may be affected by controlled sleep deprivation in healthy human subjects. We hypothesize that relevant biomarkers might be found among those conventionally related to some forms of neuronal degeneration and damage. Methods Study participants were subjected to one period of sleep deprivation (5 nights with < 4 hrs of sleep) and one period of controlled normal sleep (5 nights with 8 hrs in bed). Sleep was monitored by polysomnography and actigraphy. CSF was collected by a routine lumbar puncture in the morning following each period. CSF was also collected 3 days after the sleep deprivation period (recovery). CSF analysis included total-tau (TT), phospho-tau (PT), amyloid β42 (Aβ42) and orexin (OX). Four healthy volunteers with self-reported normal sleep and no daytime excess sleepiness were included in the current interim analysis. Results CSF concentrations of TT, PT and Aβ42 remained relatively unchanged from the normal sleep to the sleep-deprived state. In contrast, there was a pronounced increase in the concentration of TT (270 and 605 ng/L), PT (40 and 82 ng/L) and Aβ42 (1001 and 1628 ng/L) following three days of recovery. OX, on the other hand, followed an expected pattern (from 754 to 857 and 638 pg/mL, respectively) which corroborates that the observed changes in TT, PT and Aβ42 were unrelated to possible changes in CSF dynamics/volumes. Conclusions Recovery sleep following brief sleep deprivation induced pronounced changes in CSF concentrations of TT, PT and Aβ42. These markers have been associated with Alzheimer’s disease but their role in normal physiology is largely unknown. The observed changes may shed further light on sleep-associated physiological effects in the brain, particularly during recovery from sleep loss. Key Words: Alzheimer's disease, amyloid β, cerebrospinal fluid, sleep, sleep-deprivation, tau