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    1 Comment for this article
    Potential links to immune functions, CSF should be explored
    Eugene J. Koprowski, MD | Institute of Psychiatry, King's College, University of London
    The authors raise some interesting points with their research on Alzheimer’s disease pathology and sleep deprivation. There has been some speculation in the literature about Alzheimer's disease and inflammation (Akiyama, 2000) in the past. There has also been work on the relationship between Alzheimer's and immune functions (Moldofsky, 1989). Is there a link between sleep deprivation, its impact on immune function, protein transfer in the cerebral spinal fluid (CSF), and Alzheimer’s disease? This might be an area of neuropsychiatric research worth exploring. REFERENCEAkiyama, H., Barger, S., Barnum, S., Bradt, B., Bauer, J., Cole, G. M., ... & Wyss–Coray, T. (2000). Inflammation and Alzheimer’s disease. Neurobiology of aging, 21(3), 383-421Moldofsky, H., Lue, F. A., Davidson, J. R., & Gorczynski, R. (1989). Effects of sleep deprivation on human immune functions. The FASEB Journal, 3(8), 1972-1977.Reiber, H., & Felgenhauer, K. (1987). Protein transfer at the blood cerebrospinal fluid barrier and the quantitation of the humoral immune response within the central nervous system. Clinica Chimica Acta, 163(3), 319-328.
    Original Investigation
    August 2014

    Effect of 1 Night of Total Sleep Deprivation on Cerebrospinal Fluid β-Amyloid 42 in Healthy Middle-Aged Men: A Randomized Clinical Trial

    Author Affiliations
    • 1Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands
    • 2Radboud Alzheimer Center, Radboud University Medical Center, Nijmegen, the Netherlands
    • 3Department of Geriatric Medicine, Radboud University Medical Center, Nijmegen, the Netherlands
    • 4Department of Neurology, Radboud University Medical Center, Nijmegen, the Netherlands
    • 5Department of Anaesthesiology, Radboud University Medical Center, Nijmegen, the Netherlands
    • 6Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, the Netherlands
    JAMA Neurol. 2014;71(8):971-977. doi:10.1001/jamaneurol.2014.1173

    Importance  Increasing evidence suggests a relationship between poor sleep and the risk of developing Alzheimer disease. A previous study found an effect of sleep on β-amyloid (Aβ), which is a key protein in Alzheimer disease pathology.

    Objective  To determine the effect of 1 night of total sleep deprivation on cerebrospinal fluid Aβ42 protein levels in healthy middle-aged men.

    Design, Setting, and Participants  The Alzheimer, Wakefulness, and Amyloid Kinetics (AWAKE) study at the Radboud Alzheimer Center, a randomized clinical trial that took place between June 1, 2012, and October 1, 2012. Participants were cognitively normal middle-aged men (40-60 years of age) with normal sleep (n = 26) recruited from the local population.

    Interventions  Participants were randomized to 1 night with unrestricted sleep (n = 13) or 1 night of total sleep deprivation (24 hours of wakefulness) (n = 13).

    Main Outcomes and Measures  Sleep was monitored using continuous polysomnographic recording from 3 pm until 10 am. Cerebrospinal fluid samples were collected using an intrathecal catheter at defined times to compare cerebral Aβ42 concentrations between evening and morning.

    Results  A night of unrestricted sleep led to a 6% decrease in Aβ42 levels of 25.3 pg/mL (95% CI [0.94, 49.6], P = .04), whereas sleep deprivation counteracted this decrease. When accounting for the individual trajectories of Aβ42 over time, a difference of 75.8 pg/mL of Aβ42 was shown between the unrestricted sleep and sleep deprivation group (95% CI [3.4, 148.4], P = .04). The individual trajectories of evening and morning Aβ42 concentrations differed between the unrestricted sleep and sleep deprivation groups (P = .04) in contrast to stable Aβ40, tau, and total protein levels.

    Conclusions and Relevance  Sleep deprivation, or prolonged wakefulness, interferes with a physiological morning decrease in Aβ42. We hypothesize that chronic sleep deprivation increases cerebral Aβ42 levels, which elevates the risk of Alzheimer disease.

    Trial Registration  clinicaltrials.gov Identifier: NCT01194713