Effect of sleep on overnight cerebrospinal fluid amyloid β kinetics
Open accessAbstract
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 13 C 6 ‐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
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A study involving cognitively healthy adults showed that amyloid-beta in cerebrospinal fluid or the hippocampus increases after sleep deprivation or slow-wave sleep disruption.
“A study involving cognitively healthy adults showed that Aβ in CSF or the hippocampus increases after sleep deprivation or slow-wave sleep disruption, which indicates the complexity of Aβ kinetics [59, 60, 61].”
From Clinical trials of new drugs for Alzheimer disease (2020) · cites this paper as [60]
In humans, SD increases CSF levels of Aβ38, Aβ40, and Aβ42 through enhancement of Aβ production.
“In humans, SD increases CSF levels of Aβ38, Aβ40, and Aβ42 through the enhancement of Aβ production [568, 569].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [569]
In humans, sleep deprivation increases CSF Aβ levels without changing the rate of Aβ clearance.
“In a recent study of amyloid kinetics in human CSF using stable isotope labeling, there was an increase in Aβ levels following sleep deprivation but no change in rate of Aβ clearance.”
From Alzheimer Disease: An Update on Pathobiology and Treatment Strategies (2019) · cites this paper as Lucey et al., 2018
The increase in Aβ after sleep deprivation is due to increased production.
“This suggests the mechanism for increased Aβ is increased production (Lucey et al., 2018).”
From Alzheimer Disease: An Update on Pathobiology and Treatment Strategies (2019) · cites this paper as Lucey et al., 2018
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- Authors
- Lucey, B. P., Hicks, T. J., McLeland, J. S., Toedebusch, C. D., Boyd, J., Elbert, D. L., Patterson, B. W., Baty, J., Morris, J. C., Ovod, V., Mawuenyega, K. G., & Bateman, R. J.
- Affiliations
- Washington University in St. Louis (US)
- The University of Texas at Austin (US)
- Corresponding author
- Lucey, Brendan P.
- ORCID
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2018-01
- Volume
- 83
- Issue
- 1
- Pages
- 197-204
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- PMC
- PMC5876097
- OpenAlex
- W2773346142
- Cited by
- 362
- References
- 24
- Citations by year
- 2026: 46 · 2025: 35 · 2024: 64 · 2023: 39 · 2022: 25 · 2021: 52 · 2020: 50 · 2019: 37 · 2018: 14
- FWCI
- 20.44
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (UL1 TR000448, KL2 TR000450)
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- sleep, cerebrospinal fluid, amyloid-beta, sleep deprivation, sodium oxybate, Alzheimer's disease risk, amyloid-beta production, amyloid-beta 42, Aβ40
- MeSH terms
- Adult, Alzheimer Disease, Anesthetics, Circadian Rhythm, Female, Humans, Kinetics, Longitudinal Studies, Male, Middle Aged, Neuropsychological Tests, Peptide Fragments, Pilot Projects, Sleep, Sleep Wake Disorders, Sodium Oxybate, Amyloid beta-Peptides
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