Work

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

Year: 2026

Type: article

Abstract: 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 (DRN Tau ), serotonin neurons of the DRN (5‐HT Tau ), or non‐serotonergic neurons of the DRN (non5HT Tau ). 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 DRN Tau , 5‐HT Tau , and non5HT Tau disrupt sleep architecture. 5‐HT Tau and non5HT Tau 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.

Source: Alzheimer s & Dementia

DOI: 10.1002/alz.71687