Effect of sleep on overnight cerebrospinal fluid amyloid β kinetics

Abstract

Sleep disturbances are associated with future risk of Alzheimer disease. Disrupted sleep increases soluble amyloid β, suggesting a mechanism for sleep disturbances to increase Alzheimer disease risk. We tested this response in humans using indwelling lumbar catheters to serially sample cerebrospinal fluid while participants were sleep-deprived, treated with sodium oxybate, or allowed to sleep normally. All participants were infused with C -leucine to measure amyloid β kinetics. We found that sleep deprivation increased overnight amyloid β38, amyloid β40, and amyloid β42 levels by 25 to 30% via increased overnight amyloid β production relative to sleeping controls. These findings suggest that disrupted sleep increases Alzheimer disease risk via increased amyloid β production. Ann Neurol 2018;83:197-204.

Amyloid‐β immunotherapy for alzheimer disease: Is it now a long shot?

“…Patients undergoing cardiac surgery or suffering cardiac arrest also show rapid changes in Aβ levels in CSF/plasma, even infants and children, probably from a combination of mechanical trauma and anesthetic insult. An increase in CSF Aβ levels is also observed in cognitively normal adults after 1 day of sleep deprivation or slow‐wave sleep disruption . Interestingly, the increase in brain Aβ levels after chronic sleep restriction in normal adult mice is due to an upregulation of BACE pathway …”

Sleep Deprivation Affects Tau Phosphorylation in Human Cerebrospinal Fluid

“…Substantial evidence supports the idea that sleep disturbances increase the risk of AD . Levels of cerebrospinal fluid (CSF) Aβ are influenced by neuronal activity and increase ~30% with sleep deprivation in humans via increased production and release . Increased CSF Aβ concentrations due to chronic sleep disturbances have been hypothesized to be a mechanism mediating this increased risk .…”

“…How sleep deprivation and pharmacologically increased sleep affect CSF phosphorylated tau (p‐tau) is unknown. To address these questions, we measured tau and p‐tau peptide residues 151 to 406 in CSF samples collected in a previous published pilot study . We found that unphosphorylated tau increases with sleep deprivation, but changes at specific phosphorylation sites are variable.…”

Obstructive sleep apnea treatment, slow wave activity, and amyloid‐β

“…We previously showed that OSA may impair Aβ clearance and affect the relationship between slow wave activity (SWA) and Aβ. 4,5 Preliminary studies suggest slow wave activity (SWA) may modulate soluble Aβ; selective SWA deprivation increases Aβ, 6 whereas partial sleep deprivation with preserved SWA does not affect Aβ. OSA treatment increased SWA, and SWA was significantly correlated with lower Aβ after treatment.…”

“…Sleep deprivation increases Aβ levels, primarily through increased release of Aβ by neurons into the interstitial fluid (ISF). 4,5 Preliminary studies suggest slow wave activity (SWA) may modulate soluble Aβ; selective SWA deprivation increases Aβ, 6 whereas partial sleep deprivation with preserved SWA does not affect Aβ. 7 Cross-sectionally, in the normal population, increased SWA is associated with lower Aβ levels.…”