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Chronic trazodone treatment consolidates sleep, improves memory, and reduces amyloid pathology in a mouse model of Alzheimer’s disease
Arai M, Yue J, Shams E, Stevens CJ, Han H, Gibson R, Yildirim T, Feldman HH et al.. bioRxiv, 2026-08-25
Topic: Drug trials: efficacy and safety
Sleep disturbance in Alzheimer’s 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 APP NL-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.
Key findings
- 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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Study details
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 21 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design, sample size, effect reported and randomised / blinded because the record does not state it. We have no data on times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 13 of the 62 points we could judge it on, which is 21 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (bioRxiv) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Laboratory or animal study (title names “mouse”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 13 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 13 of the 62 points we could judge it on is 21 out of 100. |
| Total | 21 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Arai, M., Yue, J., Shams, E., Stevens, C. J., Han, H., Gibson, R., et al. (2026). Chronic trazodone treatment consolidates sleep, improves memory, and reduces amyloid pathology in a mouse model of Alzheimer’s disease. bioRxiv. https://doi.org/10.64898/2026.08.20.746036
Vancouver
Arai M, Yue J, Shams E, Stevens CJ, Han H, Gibson R, et al. Chronic trazodone treatment consolidates sleep, improves memory, and reduces amyloid pathology in a mouse model of Alzheimer’s disease. bioRxiv. 2026. doi:10.64898/2026.08.20.746036.
BibTeX
@article{arai2026-fb45f8a8,
author = {Arai, M. and Yue, J. and Shams, E. and Stevens, C. J. and Han, H. and Gibson, R. and Yildirim, T. and Feldman, H. H. and others},
title = {{Chronic trazodone treatment consolidates sleep, improves memory, and reduces amyloid pathology in a mouse model of Alzheimer’s disease}},
journal = {bioRxiv},
year = {2026},
doi = {10.64898/2026.08.20.746036},
url = {https://doi.org/10.64898/2026.08.20.746036}
}