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Sleep deprivation increases levels of the synaptic density marker SV2A in the human brain.

Overview

Authors: David Elmenhorst1,2, Anna L. Foerges1, Ali Gordji-Nejad1, Eva-Maria Elmenhorst3,4, Tina Kroll1, Andreas Matusch1, Simone Beer1, Bernd Neumaier5,6, Philipp Krapf5, Christoph Lerche7, Alexander Drzezga1,2,8, Andreas Bauer1,9
ORCID iDs: David Elmenhorst
  1. Institute of Neuroscience and Medicine (INM-2), Forschungszentrum Jülich, Jülich, Germany
  2. Department of Nuclear Medicine, University of Cologne, University Hospital Cologne, Cologne, Germany
  3. Institute of Aerospace Medicine, German Aerospace Center (DLR), Cologne, Germany
  4. Medical Faculty, Institute of Occupational, Social, and Environmental Medicine, RWTH Aachen University, Aachen, Germany
  5. Institute of Neuroscience and Medicine (INM-5), Forschungszentrum Jülich, Jülich, Germany
  6. Institute of Radiochemistry and Experimental Molecular Imaging (IREMB), University Hospital Cologne, Germany
  7. Institute of Neuroscience and Medicine (INM-4), Forschungszentrum Jülich, Jülich, Germany
  8. Clinical Research, German Center for Neurodegenerative Diseases (DZNE), Bonn-Cologne, Germany‌‌
  9. Medical Faculty, Department of Neurology, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
Institutions: Forschungszentrum Jülich (Germany); University of Cologne (Germany); University Hospital Cologne (Germany); Deutsches Zentrum für Luft- und Raumfahrt e. V. (DLR) (Germany); RWTH Aachen University (Germany); German Center for Neurodegenerative Diseases (Germany); Heinrich Heine University Düsseldorf (Germany)
Journal: PLoS biology, volume 24, issue 6, article e3003816
Dates: received 21 January 2026; accepted 8 May 2026; published online 23 June 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1371/journal.pbio.3003816 · PMID 42335020 · PMCID PMC13289872 · OpenAlex W7165656314
Open access: gold, a free copy (OpenAlex)
Status: code verified
Categories: PET / SPECT (modality), human (organism), cellular / molecular (subfield)
Methods: Spectral & time-frequency, Statistics, Connectivity, Physiology & signal measures
MeSH: Brain*, Membrane Glycoproteins*, Nerve Tissue Proteins*, Sleep Deprivation*, Adult, Biomarkers, Female, Humans, Male, Positron-Emission Tomography, Sleep, Synapses, Wakefulness, Young Adult (* major topic)
Journal subjects: Biology and Life Sciences, Physiology, Physiological Processes, Sleep, Medicine and Health Sciences, Neurology, Sleep Deprivation, Research and Analysis Methods, Imaging Techniques, Neuroimaging, Positron Emission Tomography, Neuroscience, Diagnostic Medicine, Diagnostic Radiology, Tomography, Radiology and Imaging, Cellular Neuroscience, Synaptic Plasticity, Developmental Neuroscience, Homeostasis, Bioassays and Physiological Analysis, Electrophysiological Techniques, Brain Electrophysiology, Electroencephalography, Electrophysiology, Neurophysiology, Brain Mapping, Clinical Medicine, Clinical Neurophysiology, Cell Biology, Cellular Structures and Organelles, Vesicles, Anatomy, Nervous System, Synapses, Synaptic Vesicles
Topic: Sleep and Wakefulness Research (Cognitive Neuroscience, Neuroscience), according to OpenAlex
Funding: Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research) (01EW1808); German Research Foundation (Grants for Collaborative Research Centre 1451 C04 and DR 445/9-1); Wellcome Leap
Citations: not cited yet (Europe PMC); 56 references in the paper

Abstract

Sleep is essential for synaptic homeostasis, a proposed mechanism whereby wakefulness leads to synaptic potentiation and sleep facilitates synaptic down-selection. Synaptic vesicle glycoprotein 2A (SV2A), whose availability is quantifiable by [¹⁸F]SynVesT-1 positron emission tomography (PET), is commonly interpreted as a proxy for synaptic density. In this randomized study, we examined 40 healthy adults (mean age 27.5 ± 6.5 years) who underwent two [¹⁸F]SynVesT-1 PET scans on consecutive days. Half of the participants were assigned to the normal sleep (i.e., control) condition and half to the sleep deprivation condition. Scans were performed at the same circadian time point, approximately 4 h after awakening in the control group and during baseline in the sleep deprivation group or after ~28 h of continuous wakefulness in the sleep deprivation group after sleep deprivation. Sleep deprivation led to significant increases in synaptic vesicle glycoprotein 2A binding in multiple brain regions, including the thalamus (+4.6%), hippocampus (+5.6%), and parietal cortex (+3.2%), whereas no changes were observed in controls. The degree of increase in synaptic vesicle glycoprotein 2A positively correlated with elevated slow wave activity during recovery sleep, a physiological marker of sleep pressure. These findings provide in vivo support for the synaptic homeostasis hypothesis in humans and suggest that synaptic vesicle glycoprotein 2A PET imaging is sensitive to sleep-wake dependent synaptic plasticity.

Trial Registration: The study was prospectively registered on 19.01.2022 here: German Clinical Trials Registry: DRKS # DRKS00027867, https://drks.de/search/en/trial/DRKS00027867.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

No file of the authors' code could be read here: it is described below, and read at its source.

Zenodo 20033920

License: CC-BY-4.0
State: the link answers, verified on 27 September 2026
Evidence: files inventoried
Size: 4 files, 0 scripts
Software Heritage: not checked
Found in: “Data Availability”
Not found: README, license file, CITATION.cff, environment file, tests, continuous integration, documentation
Availability: 1 check, the latest on 27 September 2026: the link answers (HTTP 200)
  • 27 September 2026: the link answers (HTTP 200)
At the source: doi.org/10.5281/zenodo.20033920

The paper's code and data availability statement is in the Data section.

Tracing map

Proposed by the machine: these links were found in the paper and verified at the source, without human review. The map will receive a Zenodo DOI once one of the paper's authors has validated it with their ORCID.

What the map holds:

  • 1 repository of the authors' code, each at its verified commit, with its license and how the link was found in the paper;
  • 0 scripts, each with its path and the digest of its content;
  • no match between paragraphs and code yet;
  • neither the text of the paper nor the code itself.

Its JSON (tracing-map.json) is deposited on Zenodo with its DOI once the map is validated.

Data

No dataset and no data link were found in the paper.

Data Availability

All relevant data are available within the manuscript and Supporting information files. The codes of the main statistical data analysis are available on Zenodo (https://doi.org/10.5281/zenodo.20033920). The raw data could be identified and linked to a single subject and represent a large amount of data. Researchers willing to access to the raw data should send a request at https://data.fz-juelich.de/ via https://doi.org/10.26165/JUELICH-DATA/GOTGS5. Data sharing will require evaluation of the request by the local Research Ethics Board and the signature of a data transfer agreement.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 12 authors, 14 MeSH terms, 3 funders, 56 references.

Cite

This paper

Elmenhorst, D., Foerges, A. L., Gordji-Nejad, A., Elmenhorst, E.-M., Kroll, T., Matusch, A., Beer, S., Neumaier, B., Krapf, P., Lerche, C., Drzezga, A., & Bauer, A. (2026). Sleep deprivation increases levels of the synaptic density marker SV2A in the human brain. PLoS biology, 24(6), e3003816. https://doi.org/10.1371/journal.pbio.3003816

BibTeX

@article{elmenhorst2026sleep,
author = {Elmenhorst, David and Foerges, Anna L. and Gordji-Nejad, Ali and Elmenhorst, Eva-Maria and Kroll, Tina and Matusch, Andreas and Beer, Simone and Neumaier, Bernd and Krapf, Philipp and Lerche, Christoph and Drzezga, Alexander and Bauer, Andreas},
title = {{Sleep deprivation increases levels of the synaptic density marker SV2A in the human brain}},
journal = {PLoS biology},
year = {2026},
month = jun,
volume = {24},
number = {6},
pages = {e3003816},
publisher = {PLOS},
issn = {1544-9173},
doi = {10.1371/journal.pbio.3003816},
url = {https://doi.org/10.1371/journal.pbio.3003816},
pmid = {42335020},
pmcid = {PMC13289872}
}

RIS

TY - JOUR
AU - Elmenhorst, David
AU - Foerges, Anna L.
AU - Gordji-Nejad, Ali
AU - Elmenhorst, Eva-Maria
AU - Kroll, Tina
AU - Matusch, Andreas
AU - Beer, Simone
AU - Neumaier, Bernd
AU - Krapf, Philipp
AU - Lerche, Christoph
AU - Drzezga, Alexander
AU - Bauer, Andreas
TI - Sleep deprivation increases levels of the synaptic density marker SV2A in the human brain
T2 - PLoS biology
J2 - PLoS Biol
PY - 2026
DA - 2026/06/23
VL - 24
IS - 6
SP - e3003816
SN - 1544-9173
PB - PLOS
DO - 10.1371/journal.pbio.3003816
UR - https://doi.org/10.1371/journal.pbio.3003816
LA - en
ER -

CSL-JSON

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