Slow wave sleep disruption increases cerebrospinal fluid amyloid-β levels

Abstract

See Mander et al. (doi:10.1093/awx174) for a scientific commentary on this article.Sleep deprivation increases amyloid-β, suggesting that chronically disrupted sleep may promote amyloid plaques and other downstream Alzheimer's disease pathologies including tauopathy or inflammation. To date, studies have not examined which aspect of sleep modulates amyloid-β or other Alzheimer's disease biomarkers. Seventeen healthy adults (age 35-65 years) without sleep disorders underwent 5-14 days of actigraphy, followed by slow wave activity disruption during polysomnogram, and cerebrospinal fluid collection the following morning for measurement of amyloid-β, tau, total protein, YKL-40, and hypocretin. Data were compared to an identical protocol, with a sham condition during polysomnogram. Specific disruption of slow wave activity correlated with an increase in amyloid-β40 (r = 0.610, P = 0.009). This effect was specific for slow wave activity, and not for sleep duration or efficiency. This effect was also specific to amyloid-β, and not total protein, tau, YKL-40, or hypocretin. Additionally, worse home sleep quality, as measured by sleep efficiency by actigraphy in the six nights preceding lumbar punctures, was associated with higher tau (r = 0.543, P = 0.045). Slow wave activity disruption increases amyloid-β levels acutely, and poorer sleep quality over several days increases tau. These effects are specific to neuronally-derived proteins, which suggests they are likely driven by changes in neuronal activity during disrupted sleep.

Keywords: EEG; beta-amyloid; sleep; slow wave activity; tau.

Figure 1

Decreased slow wave activity is associated with increased CSF amyloid-β. (A) Suppression of slow wave activity, as measured by the change in delta spectral power, was strongly correlated with increased amyloid-β₄₀ (r = 0.610, P = 0.009). There was no correlation between change in amyloid-β₄₀ levels and (B) total sleep time (r = −0.075, P = 0.782), (C) time in non-REM sleep (r = −0.156, P = 0.564), (D) time in REM sleep (r = −0.351 P = 0.168), or (E) sleep efficiency (r = −0.007, P = 0.978). (F) When participants are divided at the median (20 μV²×s) amount of slow wave activity disruption, the ‘responders’ to SWA disruption (blue lines) had a significant increase in amyloid-β₄₀ (n = 9, 11562 ± 2603 versus 10562 ± 2868 pg/ml, 95% confidence interval difference 315 to 1686 pg/ml, P = 0.010) while ‘non-responders’ (red lines) did not. X-axes in A–E are more negative to the right, i.e. values to the right indicate more disruption of slow wave activity or less sleep.

Figure 2

Slow wave activity disruption is not correlated with change in other CSF proteins. SWA disruption, as measured by the change in delta spectral power, was not correlated with change in (A) total protein (r = 0.098, P = 0.708), (B) YKL-40 (r = −0.199, P = 0.445), (C) tau (r = 0.000, P = 1.000), or (D) hypocretin (r = −0.250, P = 0.333). X-axes are more negative to the right, i.e. values to the right indicate more disruption of slow wave activity.

Figure 3

Worse home sleep quality over six nights is associated with increased CSF tau. Home sleep was quantified by actigraphically-measured sleep variables for the six nights prior to lumbar punctures. Valid actigraphy data were available for n = 14 participants. For consistency with other figures, sleep variables are shown as the six nights that included SWA disruption protocol night minus the six nights that included the sham condition night; however, the differences in total sleep time or sleep efficiency reflect variations in home sleep and are not related to the protocol or sham condition. For consistency with other figures, x-axes are more negative to the right, i.e. values to the right indicate less or worse sleep. (A) Worse sleep quality, as measured as the sleep efficiency, was associated with greater tau levels (r = 0.543, P = 0.045). (C) There was a strong but non-significant trend for an association between worse home sleep quality and amyloid-β₄₀ levels (r = 0.481, P = 0.081), but (E) there was no correlation between sleep quality and total protein (r = −0.218, P = 0.455). Change in home sleep quantity, as measured by actigraphically-determined total sleep time, had no correlation with (B) tau (r = 0.103, P = 0.725), (D) amyloid-β₄₀ (r = 0.218, P = 0.455), or (F) total protein (r = −0.103, P = 0.725).