Evidence map›Paper›PMID 37099634›Full record

ArticleScience translational medicine2023

Sleep deprivation exacerbates microglial reactivity and Aβ deposition in a

Samira Parhizkar, Grace Gent, Yun Chen, Nicholas Rensing, Maud Gratuze, Gregory Strout, Sanja Sviben, Eric Tycksen, Qiang Zhang, Petra Erdmann Gilmore and 14 more

Open access · greenAbstract read
In one paragraph

Article in Science translational medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
75citing papers in PubMed, 3 pooled it
13.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

75 citing papers in PubMed, 3 syntheses or guidelines pooled it, 106 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Review
  5. Article
  6. Review
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  8. Article
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  10. Review
  11. Review
  12. Caffeine reverses sleep deprivation-induced synaptic and social memory deficits via adenosine receptor modulation in the male mouse hippocampal CA2 region.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026
    Article
  13. Article
  14. Sleep fragmentation correlates with amyloid beta deposition at brain autopsy.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  15. Article
  16. Early microglial response to amyloid plaques drives sleep loss in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  17. Review
  18. Article
  19. Article
  20. Review

15 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

24 authors at 2 institutions in 1 country.

Samira ParhizkarDepartment of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA.ORCID 0000-0001-5807-190X
Grace GentDepartment of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA.
Yun ChenDepartment of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA.ORCID 0000-0003-0547-9463
Nicholas RensingDepartment of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA.
Maud GratuzeDepartment of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA.
Gregory StroutWashington University Center for Cellular Imaging, Washington University School of Medicine, St. Louis, MO, USA.ORCID 0000-0002-2027-6851
Sanja SvibenWashington University Center for Cellular Imaging, Washington University School of Medicine, St. Louis, MO, USA.ORCID 0000-0001-5918-4834
Eric TycksenGenome Technology Access Center, Washington University School of Medicine, St. Louis, MO, USA.ORCID 0000-0001-6362-0141
Qiang ZhangDepartment of Medicine, Washington University Medical School, St. Louis, MO, USA.ORCID 0000-0001-7046-4378
Petra Erdmann GilmoreDepartment of Medicine, Washington University Medical School, St. Louis, MO, USA.ORCID 0000-0002-3949-9801
Robert SprungDepartment of Medicine, Washington University Medical School, St. Louis, MO, USA.ORCID 0000-0003-2368-8859
Jim MaloneDepartment of Medicine, Washington University Medical School, St. Louis, MO, USA.ORCID 0000-0003-2199-0456
Wei ChenDepartment of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA.
Javier Remolina SerranoDepartment of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA.ORCID 0000-0002-5937-0212
Xin BaoDepartment of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA.
Choonghee LeeDepartment of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA.ORCID 0000-0001-8907-5858
Chanung WangDepartment of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA.ORCID 0000-0002-6418-3809
Eric LandsnessDepartment of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA.ORCID 0000-0003-3227-1641
James FitzpatrickWashington University Center for Cellular Imaging, Washington University School of Medicine, St. Louis, MO, USA.ORCID 0000-0002-7907-3602
Michael WongDepartment of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA.
Reid TownsendDepartment of Medicine, Washington University Medical School, St. Louis, MO, USA.ORCID 0000-0002-0753-7594
Marco ColonnaDepartment of Pathology and Immunology, Washington University, St. Louis, MO, USA.ORCID 0000-0001-5222-4987
Robert E SchmidtDepartment of Pathology and Immunology, Washington University, St. Louis, MO, USA.ORCID 0000-0002-8334-5893
David M HoltzmanDepartment of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA.ORCID 0000-0002-3400-0856
Hope Center for Neurological Disorders · USWashington University in St. Louis · US

Funding

Washington University Center for Cellular ImagingP30CA091842 · NCI · WASHINGTON UNIVERSITY · PI TIMOTHY J. EBERLEIN · 2001 to 2026
$128.0M
WU INSTITUTE OF CLINICAL AND TRANSLATIONAL SCIENCESUL1TR002345 · NCATS · WASHINGTON UNIVERSITY · PI William G. Powderly · 2017 to 2026
$97.8M
Washington University Institute of Clinical and Translational SciencesUL1TR000448 · NCATS · WASHINGTON UNIVERSITY · PI EVANOFF, BRADLEY A · 2012 to 2016
$41.4M
WUIDDRC Supplement-Supporting the health and well-being of children with intellectual and developmental disability during COVID-19 pandemicP50HD103525 · NICHD · WASHINGTON UNIVERSITY · PI JEFFREY D MILBRANDT · 2020 to 2026
$15.5M
Viral Vectors CoreP01NS074969 · NINDS · WASHINGTON UNIVERSITY · PI HOLTZMAN, DAVID M. · 2012 to 2021
$13.0M
TrainingP41GM103422 · NIGMS · WASHINGTON UNIVERSITY · PI YARASHESKI, KEVIN E · 2012 to 2019
$12.0M
Local slow wave sleep in repair and recovery after strokeK08NS109292 · NINDS · WASHINGTON UNIVERSITY · PI LANDSNESS, ERIC C · 2020 to 2024
$943k
High Sensitivity sCMOS Camera System for Transmission Electron MicroscopeS10OD032186 · OD · WASHINGTON UNIVERSITY · PI PISTON, DAVID W · 2022 to 2022
$147k
NCATS NIH HHS UL1 TR000448NCATS NIH HHS UL1 TR002345NCI NIH HHS P30 CA091842NICHD NIH HHS P50 HD103525NIGMS NIH HHS P41 GM103422NIH HHS S10 OD032186NINDS NIH HHS K08 NS109292NINDS NIH HHS P01 NS074969
6 · The paper itself

Abstract

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. 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. Unbiased transcriptome and proteome profiling provided mechanistic insights into functional pathways triggered by sleep deprivation that were unique to TREM2 and Aβ pathology and that converged on metabolic dyshomeostasis. Our findings highlight that sleep deprivation directly affects microglial reactivity, for which TREM2 is required, by altering the metabolic ability to cope with the energy demands of prolonged wakefulness, leading to further Aβ deposition, and underlines the importance of sleep modulation as a promising future therapeutic approach.

Indexed as

Alzheimer DiseaseAmyloidosisAmyloid beta-PeptidesAnimalsBrainDisease Models, AnimalMembrane GlycoproteinsMiceMicrogliaPlaque, AmyloidReceptors, ImmunologicSleep DeprivationAmyloid beta-PeptidesMembrane GlycoproteinsReceptors, ImmunologicTrem2 protein, mouse

Identifiers

PMID37099634
PMCPMC10449561
OpenAlexW4367059832

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.