Amyloid beta-independent sleep markers associated with early regional tau burden and cortical thinning

Sleep is crucial for memory consolidation and the clearance of toxic proteins associated with Alzheimer's disease (AD). We examined the association between sleep characteristics and imaging biomarkers of early amyloid beta (Aβ) and tau pathology as well as neurodegeneration in brain regions known to be affected in the incipient stages of AD.

Thirty-nine cognitively unimpaired (CU) participants of the Harvard Aging Brain Study underwent at-home polysomnography as well as tau positron emission tomography (flortaucipir-PET), amyloid PET (Pittsburgh compound B [PiB]-PET), and magnetic resonance imaging-derived assessment of cortical thickness (CT).

Increased N1 sleep was associated with a higher tau PET signal (β = 0.009, p = 0.001) and lower CT in the temporal composite region of interest (β = -0.017, p = 0.007). Decreased slow-wave sleep (SWS) was associated with higher tau burden in the temporal composite (β = -0.008, p = 0.005) and lower CT (β = 0.008, p = 0.002), even after controlling for global PiB-PET.

In CU older adults, lower SWS and higher N1 sleep were associated with higher tau burden and lower CT in brain regions associated with early tau deposition and vulnerable to AD-related neurodegeneration through mechanisms dissociable from amyloid deposition.

We report the results of an observational study, which leveraged -a well-characterized cohort of healthy aging (Harvard Aging Brain Study) by adding in-home full polysomnograms.By adding at-home polysomnograms to this unique and deeply phenotyped cohort, we examined variations in sleep architecture that are associated with Alzheimer's disease (AD) pathologic changes.Our results confirmed the association of sleep changes with early tau and cortical neurodegenerative changes that were independent of amyloid.The results will be of importance in monitoring sleep-related variations in relation to the natural history of AD pathology and in designing sleep-focused clinical trials.