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Sleep deprivation exacerbates microglial reactivity and Aβ deposition in a TREM2-dependent manner in mice
Parhizkar S, Gent G, Chen Y, Rensing N, Gratuze M, Strout G, Sviben S, Tycksen E et al.. Science translational medicine, 2023-04-26
Topic: Brain proteins, microglia and lab models
Sleep loss is associated with cognitive decline in the aging population and is a risk factor for Alzheimer's disease (AD). Considering the crucial role of immunomodulating genes such as that encoding the triggering receptor expressed on myeloid cells type 2 (TREM2) in removing pathogenic amyloid-β (Aβ) plaques and regulating neurodegeneration in the brain, our aim was to investigate whether and how sleep loss influences microglial function in mice. We chronically sleep-deprived wild-type mice and the 5xFAD mouse model of cerebral amyloidosis, expressing either the humanized TREM2 common variant, the loss-of-function R47H AD-associated risk variant, or without TREM2 expression.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Parhizkar, S., Gent, G., Chen, Y., Rensing, N., Gratuze, M., Strout, G., et al. (2023). Sleep deprivation exacerbates microglial reactivity and Aβ deposition in a TREM2-dependent manner in mice. Science translational medicine. https://doi.org/10.1126/scitranslmed.ade6285
Vancouver
Parhizkar S, Gent G, Chen Y, Rensing N, Gratuze M, Strout G, et al. Sleep deprivation exacerbates microglial reactivity and Aβ deposition in a TREM2-dependent manner in mice. Science translational medicine. 2023. doi:10.1126/scitranslmed.ade6285. PMID: 37099634.
BibTeX
@article{parhizkar2023-37099634,
author = {Parhizkar, S. and Gent, G. and Chen, Y. and Rensing, N. and Gratuze, M. and Strout, G. and Sviben, S. and Tycksen, E. and others},
title = {{Sleep deprivation exacerbates microglial reactivity and Aβ deposition in a TREM2-dependent manner in mice}},
journal = {Science translational medicine},
year = {2023},
doi = {10.1126/scitranslmed.ade6285},
pmid = {37099634},
url = {https://doi.org/10.1126/scitranslmed.ade6285}
}
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Key findings
- Considering the crucial role of immunomodulating genes such as that encoding the triggering receptor expressed on myeloid cells type 2 (TREM2) in removing pathogenic amyloid-β (Aβ) plaques and regulating neurodegeneration in the brain, our aim was to investigate whether and how sleep loss influences microglial function in mice.
- We chronically sleep-deprived wild-type mice and the 5xFAD mouse model of cerebral amyloidosis, expressing either the humanized TREM2 common variant, the loss-of-function R47H AD-associated risk variant, or without TREM2 expression.
- Sleep deprivation not only enhanced TREM2-dependent Aβ plaque deposition compared with 5xFAD mice with normal sleeping patterns but also induced microglial reactivity that was independent of the presence of parenchymal Aβ plaques.
- We investigated lysosomal morphology using transmission electron microscopy and found abnormalities particularly in mice without Aβ plaques and also observed lysosomal maturation impairments in a TREM2-dependent manner in both microglia and neurons, suggesting that changes in sleep modified neuro-immune cross-talk.
Why it matters
In mice, chronic sleep deprivation worsened microglial reactivity and amyloid-beta deposition in a TREM2-dependent manner. It is an animal study, so it does not show that improving sleep prevents or treats Alzheimer's disease in people.
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Study details
- Evidence strengthLow
How this study scored 51/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Science translational medicine) |
| Journal's citation record | 3 / 4 | Science Translational Medicine: journal h-index 365 (OpenAlex, 2026-10-29) |
| 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 | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2023 — within 6 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 “mice”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 129 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 25.8 citations a year over 5 year(s) since 2023 |
| Impact for its field and year | 4 / 6 | Cited 10.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 4 other studies in this library |
| Still being cited | 3 / 4 | Cited 119 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author David M. Holtzman: h-index 206 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Washington University in St. Louis: institution h-index 1,962 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 37099634) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 51 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1126/scitranslmed.ade6285
- PubMed: 37099634
- Original source →
- Free full text: PubMed Central →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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