Sleep oscillation-specific associations with Alzheimer’s disease CSF biomarkers: novel roles for sleep spindles and tau

Abstract

Background Based on associations between sleep spindles, cognition, and sleep-dependent memory processing, here we evaluated potential relationships between levels of CSF Aβ 42 , P-tau, and T-tau with sleep spindle density and other biophysical properties of sleep spindles in a sample of cognitively normal elderly individuals. Methods One-night in-lab nocturnal polysomnography (NPSG) and morning to early afternoon CSF collection were performed to measure CSF Aβ 42 , P-tau and T-tau. Seven days of actigraphy were collected to assess habitual total sleep time. Results Spindle density during NREM stage 2 (N2) sleep was negatively correlated with CSF Aβ 42 , P-tau and T-tau. From the three, CSF T-tau was the most significantly associated with spindle density, after adjusting for age, sex and ApoE4. Spindle duration, count and fast spindle density were also negatively correlated with T-tau levels. Sleep duration and other measures of sleep quality were not correlated with spindle characteristics and did not modify the associations between sleep spindle characteristics and the CSF biomarkers of AD. Conclusions Reduced spindles during N2 sleep may represent an early dysfunction related to tau, possibly reflecting axonal damage or altered neuronal tau secretion, rendering it a potentially novel biomarker for early neuronal dysfunction. Given their putative role in memory consolidation and neuroplasticity, sleep spindles may represent a mechanism by which tau impairs memory consolidation, as well as a possible target for therapeutic interventions in cognitive decline. Electronic supplementary material The online version of this article (10.1186/s13024-019-0309-5) contains supplementary material, which is available to authorized users.

Local Sleep and Alzheimer’s Disease Pathophysiology

“…In human studies, sleep spindle density and duration, but not SWA, are negatively associated with CSF-measured total and hyperphosphorylated tau levels in cognitively asymptomatic older adults (Kam et al, 2019). A similar finding was observed with slow wave-sleep spindle coupling strength, over frontal and parietal derivations, in relation to MTL tau burden in cognitively asymptomatic older adults (Figures 1B,D) (Winer et al, 2019).…”

Characterizing Sleep Spindles in Sheep

“…It has been suggested, however, that by taking advantage of the high intra-individual night-to-night consistency it would be possible to use spindles to track progression of neurodegeneration longitudinally (Clawson et al, 2016;Seibt et al, 2016). Spindle density has been reported to change during aging (Purcell et al, 2017) as well as during neurodegenerative diseases such as Parkinson's disease (Emser et al, 1988), Alzheimer's disease (Kam et al, 2019), and Huntington's disease (Wiegand et al, 1991). Indeed, there is post hoc evidence to suggest that sleep spindles can be used as early predictors of neurodegenerative disorders (Latreille et al, 2015).…”

Is Sleep Disruption a Cause or Consequence of Alzheimer’s Disease? Reviewing Its Possible Role as a Biomarker

“…This correlation was especially strong with t-tau as well as with the ratio of t-tau/Aβ. Nevertheless, CSF tau measures did not correlate with total sleep time nor with sleep quality [120]. So, spindle density in N2 could be another candidate as AD biomarker.…”

“…Interestingly, of the three, t-tau was the one that most significantly associated with sleep spindle density, after adjusting for age, sex and ApoE4. Moreover, spindle duration, count, and density of fast spindles also correlated negatively with t-tau levels [120]. Lastly, Holth et al (2019) found that the sleep-wake cycle and sleep deprivation influenced the amount of tau in interstitial fluid and CSF, both in experimental animals and in humans.…”

“…Moreover, they found a stronger relationship between tau and SWA than between Aβ and SWA, leading them to conclude that tauopathy, rather than Aβ, correlates with sleep disturbances in asymptomatic or mildly symptomatic AD [119]. In another study by Kam et al (2019), NREM sleep correlated with the amount of CSF Aβ, p-tau, and t-tau. Interestingly, of the three, t-tau was the one that most significantly associated with sleep spindle density, after adjusting for age, sex and ApoE4.…”