Evidence map›Paper›PMID 40530247›Full record

ArticleAPL bioengineering2025

Astrocyte-driven vasoconstriction impairs glymphatic clearance in a human tauopathy-on-chip model.

Rena Park, Yansong Peng, Aria R Yslas, Esak Lee

Abstract read
In one paragraph

Article in APL bioengineering, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Review
  2. Regional astrocyte dysregulation and altered glymphatic-related markers in Alzheimer's disease frontal cortex.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  3. Review
  4. Article
  5. Review
  6. Review
  7. Article
  8. 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

4 authors.

Rena ParkNancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, New York 14853, USA.ORCID https://orcid.org/0009-0001-9921-5970
Yansong PengNancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, New York 14853, USA.ORCID https://orcid.org/0000-0002-5855-5573
Aria R YslasNancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, New York 14853, USA.
Esak LeeNancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, New York 14853, USA.ORCID https://orcid.org/0000-0002-5328-6677

Funding

Regulation of Lymphatic Endothelial Cell Junction and DrainageR01HL165135 · NHLBI · CORNELL UNIVERSITY · PI Esak Lee · 2022 to 2026
$2.5M
Tissue-Engineered Models of Lymphatic Drainage in Breast CancerR01CA279560 · NCI · CORNELL UNIVERSITY · PI Esak Lee · 2023 to 2026
$1.6M
NCI NIH HHS R01 CA279560NHLBI NIH HHS R01 HL165135
6 · The paper itself

Abstract

The glymphatic system is a critical pathway for clearing metabolic waste from the brain by mediating cerebrospinal fluid and interstitial fluid exchange. In Alzheimer's disease (AD), tau protein accumulation is strongly associated with impaired glymphatic clearance, yet the underlying mechanism remains poorly defined. In this study, we employed a three-dimensional human glymphatics-on-chip model to investigate fluid transport and mass clearance in a brain-mimetic extracellular matrix containing engineered blood vessels (BV) surrounded by primary astrocytes. We found that phosphorylated tau (p-tau) induced morphological transformation of astrocytes into a hypertrophic, hypercontractile state, leading to astrocyte-mediated vasoconstriction and impaired glymphatic clearance. Notably, p-tau did not affect blood endothelial cells directly, implicating astrocyte-dependent mechanisms in glymphatic deregulation. Pharmacological inhibition of non-muscle myosin II with blebbistatin reversed astrocytic hypercontractility, restored BV diameters, and rescued glymphatic function. These findings elucidate a glial-specific mechanism of tau-induced glymphatic dysfunction and underscore astrocytic contractility as a promising therapeutic target in AD.

Identifiers

PMID40530247
PMCPMC12173474

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.