Abstract
ObjectiveDisrupted sleep increases CSF levels of tau and β-amyloid (Aβ) and is associated with an increased risk of Alzheimer disease (AD). Our aim was to determine whether acute sleep loss alters diurnal profiles of plasma-based AD-associated biomarkers.MethodsIn a 2-condition crossover study, 15 healthy young men participated in 2 standardized sedentary in-laboratory conditions in randomized order: normal sleep vs overnight sleep loss. Plasma levels of total tau (t-tau), Aβ40, Aβ42, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) were assessed using ultrasensitive single molecule array assays or ELISAs, in the fasted state in the evening prior to, and in the morning after, each intervention.ResultsIn response to sleep loss (+17.2%), compared with normal sleep (+1.8%), the evening to morning ratio was increased for t-tau (p = 0.035). No changes between the sleep conditions were seen for levels of Aβ40, Aβ42, NfL, or GFAP (all p > 0.10). The AD risk genotype rs4420638 did not significantly interact with sleep loss–related diurnal changes in plasma levels of Aβ40 or Aβ42 (p > 0.10). Plasma levels of Aβ42 (−17.1%) and GFAP (−12.1%) exhibited an evening to morning decrease across conditions (p < 0.05).ConclusionsOur exploratory study suggests that acute sleep loss results in increased blood levels of t-tau. These changes provide further evidence that sleep loss may have detrimental effects on brain health even in younger individuals. Larger cohorts are warranted to delineate sleep vs circadian mechanisms, implications for long-term recurrent conditions (e.g., in shift workers), as well as interactions with other lifestyle and genetic factors.
Highlights
In a 2-condition crossover study, 15 healthy young men participated in 2 standardized sedentary in-laboratory conditions in randomized order: normal sleep vs overnight sleep loss
No changes between the sleep conditions were seen for levels of Aβ40, Aβ42, neurofilament light chain (NfL), or glial fibrillary acidic protein (GFAP)
Similar to recent findings based on CSF sampling under conditions of acute sleep loss,[8] the evening to morning change in average plasma levels of tau exhibited an increase following sleep loss, compared with normal sleep (p = 0.0345; Bayes factor (BF) = 2.05)
Summary
In a 2-condition crossover study, 15 healthy young men participated in 2 standardized sedentary in-laboratory conditions in randomized order: normal sleep vs overnight sleep loss. Eligible participants were invited during 2012–2013 to participate in a within-subject crossover design study. One participant was unable to complete his second session due to scheduling conflicts. Another participant was unable to sleep during his sleep session and was excluded. 15 healthy normal-weight men (age 22.3 ± 0.5 years, body mass index 22.6 ± 0.5 kg/m2, as reported in reference 12) participated in both nighttime interventions, in randomized order, i.e., a night of normal sleep compared with a night of sleep loss. Study size was chosen based on similar studies in the field of biomarker analysis related to neuronal health (c.f. references 11 and 13) and the field of sleep metabolism (c.f. reference 14)
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