Chronic trazodone treatment consolidates sleep, improves memory, and reduces amyloid pathology in a mouse model of Alzheimers disease
- 1Simon Fraser University
Abstract
Sleep disturbance in Alzheimers disease (AD), particularly the reduction of slow wave sleep (SWS), has been proposed as a novel therapeutic target, with disease-modifying potential. Trazodone, an antidepressant with robust SWS-promoting properties, is currently the most prescribed sleep-promoting medication in the United States. Here, we demonstrate that chronic trazodone administration consolidates sleep in the APPNL-F knock-in mouse model of AD, increasing NREM sleep duration and slow wave power during the rest phase while promoting wake during the active phase. These sleep consolidating effects were accompanied by lower regional glial activation and amyloid burden, particularly in male mice. Most notably, hippocampal amyloid plaque burden was 45% lower in mice treated from 14 to 16 months of age than in vehicle-treated controls. Chronic trazodone treatment was also associated with better short-term and long-term recognition memory. Together, these findings support the potential of repurposing trazodone as a well-tolerated, disease-modifying therapeutic for AD, capable of enhancing sleep quality, improving cognition, and lowering AD-relevant neuropathology.
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BibTeX
@misc{arai2026chronic,
title = {{Chronic trazodone treatment consolidates sleep, improves memory, and reduces amyloid pathology in a mouse model of Alzheimers disease}},
author = {M. Arai and J. Yue and E. Shams and C. J. Stevens and H. Han and R. Gibson and T. Yildirim and H. H. Feldman and C. L. Wellington and B. A. Kent},
howpublished = {bioRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.20.746036},
url = {https://www.biorxiv.org/content/10.64898/2026.08.20.746036v2},
note = {CC BY-ND},
}
RIS
TY - UNPB
TI - Chronic trazodone treatment consolidates sleep, improves memory, and reduces amyloid pathology in a mouse model of Alzheimers disease
AU - M. Arai
AU - J. Yue
AU - E. Shams
AU - C. J. Stevens
AU - H. Han
AU - R. Gibson
AU - T. Yildirim
AU - H. H. Feldman
AU - C. L. Wellington
AU - B. A. Kent
PY - 2026
DA - 2026/08/20
PB - bioRxiv
DO - 10.64898/2026.08.20.746036
UR - https://www.biorxiv.org/content/10.64898/2026.08.20.746036v2
AB - Sleep disturbance in Alzheimers disease (AD), particularly the reduction of slow wave sleep (SWS), has been proposed as a novel therapeutic target, with disease-modifying potential. Trazodone, an antidepressant with robust SWS-promoting properties, is currently the most prescribed sleep-promoting medication in the United States. Here, we demonstrate that chronic trazodone administration consolidates sleep in the APPNL-F knock-in mouse model of AD, increasing NREM sleep duration and slow wave power during the rest phase while promoting wake during the active phase. These sleep consolidating effects were accompanied by lower regional glial activation and amyloid burden, particularly in male mice. Most notably, hippocampal amyloid plaque burden was 45% lower in mice treated from 14 to 16 months of age than in vehicle-treated controls. Chronic trazodone treatment was also associated with better short-term and long-term recognition memory. Together, these findings support the potential of repurposing trazodone as a well-tolerated, disease-modifying therapeutic for AD, capable of enhancing sleep quality, improving cognition, and lowering AD-relevant neuropathology.
ER -