Dorsal raphe tau pathology disrupts sleep-wake orchestration and sleep architecture in a sex-specific manner.

INTRODUCTION

Sleep disturbances are frequent symptoms of Alzheimer's disease (AD), mirrored by early pathology in the dorsal raphe nucleus (DRN). Whether early DRN pathology can drive sleep disturbances, and the relative contributions of serotonin (5-HT) and sex, has not been directly tested.

METHODS

We isolate tau pathology to whole DRN (DRNTau), serotonin neurons of the DRN (5-HTTau), or non-serotonergic neurons of the DRN (non5HTTau). We use longitudinal EEG recordings, in male and female mice, to determine the contributions of DRN neuronal subtypes to sleep disruption within the context of prodromal AD.

RESULTS

DRNTau, 5-HTTau, and non5HTTau disrupt sleep architecture. 5-HTTau and non5HTTau further disrupt sleep-wake orchestration and exhibit sex-dependent alterations that coincide with changes in delta wave power.

DISCUSSION: Tau-mediated sleep dysfunction may be driven by various cellular subtypes of the DRN, are primarily sexually divergent, and may resultant in changes in 5-HT activity and relative spectral brain wave contributions.