Research ArticleAlzheimer’s Disease

Reduced non–rapid eye movement sleep is associated with tau pathology in early Alzheimer’s disease

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Science Translational Medicine  09 Jan 2019:
Vol. 11, Issue 474, eaau6550
DOI: 10.1126/scitranslmed.aau6550

Losing sleep over Alzheimer’s disease

In patients with Alzheimer’s disease (AD), amyloid-β (Aβ) plaques and tau protein tangles accumulate in the brain long before the appearance of clinical symptoms. Early intervention is critical for slowing neurodegeneration and disease progression. Therefore, reliable markers of early AD are needed. Lucey et al. analyzed sleep patterns in aging cognitively normal subjects and showed that non–rapid eye movement (NREM) sleep negatively correlated with tau pathology and Aβ deposition in several brain areas. The results show that alterations in NREM sleep may be an early indicator of AD pathology and suggest that noninvasive sleep analysis might be useful for monitoring patients at risk for developing AD.


In Alzheimer’s disease (AD), deposition of insoluble amyloid-β (Aβ) is followed by intracellular aggregation of tau in the neocortex and subsequent neuronal cell loss, synaptic loss, brain atrophy, and cognitive impairment. By the time even the earliest clinical symptoms are detectable, Aβ accumulation is close to reaching its peak and neocortical tau pathology is frequently already present. The period in which AD pathology is accumulating in the absence of cognitive symptoms represents a clinically relevant time window for therapeutic intervention. Sleep is increasingly recognized as a potential marker for AD pathology and future risk of cognitive impairment. Previous studies in animal models and humans have associated decreased non–rapid eye movement (NREM) sleep slow wave activity (SWA) with Aβ deposition. In this study, we analyzed cognitive performance, brain imaging, and cerebrospinal fluid (CSF) AD biomarkers in participants enrolled in longitudinal studies of aging. In addition, we monitored their sleep using a single-channel electroencephalography (EEG) device worn on the forehead. After adjusting for multiple covariates such as age and sex, we found that NREM SWA showed an inverse relationship with AD pathology, particularly tauopathy, and that this association was most evident at the lowest frequencies of NREM SWA. Given that our study participants were predominantly cognitively normal, this suggested that changes in NREM SWA, especially at 1 to 2 Hz, might be able to discriminate tau pathology and cognitive impairment either before or at the earliest stages of symptomatic AD.

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