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Chronic orexin receptor antagonism is associated with rescued sleep and agitation-like behaviour in tau transgenic PS19 mice, but sex-dependently improved cognition
Kron JO, Keenan RJ, Metha J, Daykin H, Potts Y, Ch’ng C, Elliot JG, Allocca JG et al.. Authorea Preprints, 2026-07-25
Topic: Disease mechanisms in lab and animal studies
DORA-22 and MK-1064 rescued tauopathy-related sleep loss, and reduced agitation-like locomotion and stress-induced hyperthermic responses. DORA-22 and MK-1064 rescued Barnes maze cognitive performance to near WT levels in male PS19 mice. However, female PS19s receiving either DORA-22 or MK-1064 demonstrated poorer cognition compared to either WTs or their untreated controls, despite restoration of sleep. MK-1064 reduced tau pathology in the tuberomammillary nucleus. Tauopathy may sex-dependently decouple the relationship between sleep and cognition. DORAs and 2-SORAs may have therapeutic potential for improving AD outcomes associated with tauopathy. Future clinical studies should examine the effects of biological sex on responses to ORAs in tauopathies.
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APA 7th
Kron, J. O., Keenan, R. J., Metha, J., Daykin, H., Potts, Y., Ch’ng, C., et al. (2026). Chronic orexin receptor antagonism is associated with rescued sleep and agitation-like behaviour in tau transgenic PS19 mice, but sex-dependently improved cognition. Authorea Preprints. https://doi.org/10.22541/authorea.15006549/v1
Vancouver
Kron JO, Keenan RJ, Metha J, Daykin H, Potts Y, Ch’ng C, et al. Chronic orexin receptor antagonism is associated with rescued sleep and agitation-like behaviour in tau transgenic PS19 mice, but sex-dependently improved cognition. Authorea Preprints. 2026. doi:10.22541/authorea.15006549/v1.
BibTeX
@article{kron2026-9fc2d73f,
author = {Kron, J. O. and Keenan, R. J. and Metha, J. and Daykin, H. and Potts, Y. and Ch’ng, C. and Elliot, J. G. and Allocca, J. G. and others},
title = {{Chronic orexin receptor antagonism is associated with rescued sleep and agitation-like behaviour in tau transgenic PS19 mice, but sex-dependently improved cognition}},
journal = {Authorea Preprints},
year = {2026},
doi = {10.22541/authorea.15006549/v1},
url = {https://doi.org/10.22541/authorea.15006549/v1}
}
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.
Key findings
- DORA-22 and MK-1064 rescued tauopathy-related sleep loss, and reduced agitation-like locomotion and stress-induced hyperthermic responses.
- DORA-22 and MK-1064 rescued Barnes maze cognitive performance to near WT levels in male PS19 mice.
- However, female PS19s receiving either DORA-22 or MK-1064 demonstrated poorer cognition compared to either WTs or their untreated controls, despite restoration of sleep.
- MK-1064 reduced tau pathology in the tuberomammillary nucleus.
- Tauopathy may sex-dependently decouple the relationship between sleep and cognition.
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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 (Authorea Preprints) |
| 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 “transgenic”) — 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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