Evidence map›Paper›PMID 41593094›Full record

Trial reportNature communications2026

The glymphatic system clears amyloid beta and tau from brain to plasma in humans.

Paul Dagum, Donald L Elbert, Laurent Giovangrandi, Tarandeep Singh, Venky V Venkatesh, Alejandro Corbellini, Robert M Kaplan, Swati Rane Levendovszky, Elizabeth Ludington, Kevin Yarasheski and 4 more

Abstract readRandomized Controlled Trial
In one paragraph

Trial report in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
–field-weighted citation impact
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

36 citing papers in PubMed.

  1. Review
  2. High frame ratebioRxiv : the preprint server for biology · 2026
    Article
  3. Article
  4. Article
  5. Article
  6. Synergistic association of insomnia and anxiety with cognitive impairment and dementia in older adults.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  7. The glymphatic system and Parkinson's disease: a narrative review.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026
    Review
  8. Article
  9. Article
  10. Dorsal raphe tau pathology disrupts sleep-wake orchestration and sleep architecture in a sex-specific manner.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  11. Article
  12. Article
  13. Sleep fragmentation correlates with amyloid beta deposition at brain autopsy.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  14. Article
  15. Review
  16. Review
  17. Article
  18. Article
  19. Review
  20. Review
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

14 authors.

Paul DagumApplied Cognition Inc., Redwood City, CA, USA. paul@appliedcognition.com.ORCID http://orcid.org/0000-0002-9843-4039
Donald L ElbertDepartment of Neurology, University of Washington School of Medicine, Seattle, WA, USA.ORCID http://orcid.org/0000-0001-6480-9536
Laurent GiovangrandiApplied Cognition Inc., Redwood City, CA, USA.
Tarandeep SinghApplied Cognition Inc., Redwood City, CA, USA.
Venky V VenkateshC2N Diagnostics, St. Louis, MO, USA.
Alejandro CorbelliniApplied Cognition Inc., Redwood City, CA, USA.
Robert M KaplanClinical Excellence Research Center, Stanford University School of Medicine, Stanford, CA, USA.
Swati Rane LevendovszkyDepartment of Radiology, University of Washington School of Medicine, Seattle, WA, USA.
Elizabeth LudingtonEpalla Consulting, San Diego, CA, USA.
Kevin YarasheskiC2N Diagnostics, St. Louis, MO, USA.ORCID http://orcid.org/0000-0001-5436-2451
Jeffrey LowenkronThe Villages Health System, The Villages, Villages, FL, USA.
Carla VandeWeerdUniversity of Florida Precision Health Research Center, University of Florida, Gainesville, FL, USA.
Miranda M LimVISN 20 Northwest Mental Illness Research, Education and Clinical Center (MIRECC), VA Portland Health Care System, Portland, OR, USA.
Jeffrey J IliffDepartment of Neurology, University of Washington School of Medicine, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-6910-0080

Funding

University of Washington Alzheimer's Disease Research CenterP30AG066509 · NIA · UNIVERSITY OF WASHINGTON · PI Thomas J. Grabowski · 2020 to 2026
$29.0M
Research Education ComponentP30AG066518 · NIA · OREGON HEALTH & SCIENCE UNIVERSITY · PI Zachary Beattie · 2020 to 2026
$28.6M
Role of Sleep Disruption after mTBI as a Driver of Chronic Post-traumatic HeadacheR01NS129573 · NINDS · SEATTLE INST FOR BIOMEDICAL/CLINICAL RES · PI Jeffrey J Iliff, Andrew F Russo · 2023 to 2026
$2.4M
NIA NIH HHS P30 AG066509NIA NIH HHS P30 AG066518NINDS NIH HHS R01 NS129573
6 · The paper itself

Abstract

Dysfunction of the glymphatic system has been proposed as a mechanistic link between sleep disruption and Alzheimer's disease (AD). In animal models, glymphatic impairment alone can drive AD pathology. Whether this system clears amyloid beta (Aβ) and tau in humans remains unknown. In a randomized crossover trial with 39 participants, we found that glymphatic clearance during normal sleep increased morning plasma levels of AD biomarkers compared to sleep deprivation. Participants underwent overnight monitoring using an investigational device that measured dynamic changes in synaptic-metabolic release and glymphatic activity. The observed changes mirrored predictions from a multicompartment model based on published data on Aβ and tau release and clearance. Our findings indicate that sleep-active physiological processes, particularly reduced brain parenchymal resistance, enhance overnight glymphatic clearance of AD biomarkers to plasma. These results support a key role for glymphatic function in AD pathophysiology and suggest its enhancement as a potential therapeutic strategy to slow disease progression.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesBrainGlymphatic Systemtau ProteinsAdultAgedBiomarkersCross-Over StudiesFemaleHumansMaleMiddle AgedSleepSleep DeprivationAmyloid beta-PeptidesBiomarkersMAPT protein, humantau Proteins

Identifiers

PMID41593094
PMCPMC12847902

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

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.