Evidence map›Paper›PMID 40987419›Full record

ArticleNeurobiology of disease2025

Regional differences in astrocytic Aquaporin-4 protein levels and distribution in aging and Alzheimer's disease in down syndrome.

Cherie A Stringer, Haley K S Miyasato, Kevin A Camey, Krina A Ghadia, Elizabeth J Andrews, Phong T Ngo, Jesse R Pascual, Sierra T Wright, Justine A Silva, Brianna M Gawronski and 13 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurobiology of disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Review
  2. Influence of an AQP4 haplotype and sleep duration on early Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  3. Article
  4. Article
  5. Article
  6. Use of anti-amyloid-β monoclonal antibodies in persons with Down syndrome Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Review
  7. 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

23 authors.

Cherie A StringerDepartment of Pathology and Laboratory Medicine, University of California, Irvine, CA, USA. Electronic address: clepe1@uci.edu.
Haley K S MiyasatoDepartment of Pathology and Laboratory Medicine, University of California, Irvine, CA, USA. Electronic address: Haley.miyasato@wsu.edu.
Kevin A CameyDepartment of Pathology and Laboratory Medicine, University of California, Irvine, CA, USA. Electronic address: camey@usc.edu.
Krina A GhadiaDepartment of Pathology and Laboratory Medicine, University of California, Irvine, CA, USA. Electronic address: kghadia@uci.edu.
Elizabeth J AndrewsDepartment of Pathology and Laboratory Medicine, University of California, Irvine, CA, USA. Electronic address: ejandrews@uci.edu.
Phong T NgoDepartment of Pathology and Laboratory Medicine, University of California, Irvine, CA, USA.
Jesse R PascualDepartment of Pathology and Laboratory Medicine, University of California, Irvine, CA, USA. Electronic address: jesserp@uci.edu.
Sierra T WrightDepartment of Pathology and Laboratory Medicine, University of California, Irvine, CA, USA; Alzheimer's Disease Research Center, University of California, Irvine, CA, USA; Alzheimer Biomarker Consortium-Down Syndrome, University of California, Irvine, CA, USA. Electronic address: stwright@uci.edu.
Justine A SilvaDepartment of Pathology and Laboratory Medicine, University of California, Irvine, CA, USA; Alzheimer's Disease Research Center, University of California, Irvine, CA, USA; Alzheimer Biomarker Consortium-Down Syndrome, University of California, Irvine, CA, USA; Center for Aging Research in Down Syndrome, University of California, Irvine, CA, USA. Electronic address: justias3@uci.edu.
Brianna M GawronskiAlzheimer's Disease Research Center, University of California, Irvine, CA, USA; University of California, Irvine Institute for Memory Impairments and Neurological Disorders, CA, USA. Electronic address: bgawrons@uci.edu.
Lourdes GonzalezAlzheimer's Disease Research Center, University of California, Irvine, CA, USA; University of California, Irvine Institute for Memory Impairments and Neurological Disorders, CA, USA. Electronic address: lourdeg3@uci.edu.
Kevin A WoodAlzheimer's Disease Research Center, University of California, Irvine, CA, USA; University of California, Irvine Institute for Memory Impairments and Neurological Disorders, CA, USA. Electronic address: woodka@uci.edu.
Michael J PhelanDepartment of Pathology and Laboratory Medicine, University of California, Irvine, CA, USA. Electronic address: phelanm@uci.edu.
Florence LaiAlzheimer Biomarker Consortium-Down Syndrome, University of California, Irvine, CA, USA; Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: flai@partners.org.
Frederick A SchmittAlzheimer Biomarker Consortium-Down Syndrome, University of California, Irvine, CA, USA; Geriatric Research Education and Clinical Center, VA Pittsburgh Healthcare System, Pittsburgh, PA, USA. Electronic address: fascom@uky.edu.
Jordan P HarpAlzheimer Biomarker Consortium-Down Syndrome, University of California, Irvine, CA, USA; Geriatric Research Education and Clinical Center, VA Pittsburgh Healthcare System, Pittsburgh, PA, USA. Electronic address: jordanharp@uky.edu.
Adam M BrickmanAlzheimer Biomarker Consortium-Down Syndrome, University of California, Irvine, CA, USA; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Gertrude H. Sergievsky Center, and the Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA. Electronic address: amb2139@cumc.columbia.edu.
Patrick J LaoAlzheimer Biomarker Consortium-Down Syndrome, University of California, Irvine, CA, USA; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Gertrude H. Sergievsky Center, and the Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA. Electronic address: pjl2133@cumc.columbia.edu.
Mark E MapstoneAlzheimer's Disease Research Center, University of California, Irvine, CA, USA; University of California, Irvine Institute for Memory Impairments and Neurological Disorders, CA, USA; Alzheimer Biomarker Consortium-Down Syndrome, University of California, Irvine, CA, USA; Department of Neurology and Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Electronic address: mark.mapstone@uci.edu.
Julia K KoflerAlzheimer Biomarker Consortium-Down Syndrome, University of California, Irvine, CA, USA; University of Kentucky Department of Neurology, Lexington, KY, USA. Electronic address: koflerjk@upmc.edu.
Milos D IkonomovicAlzheimer Biomarker Consortium-Down Syndrome, University of California, Irvine, CA, USA; Department of Neurology and Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Geriatric Research Education and Clinical Center, VA Pittsburgh Healthcare System, Pittsburgh, PA, USA. Electronic address: ikonomovimd@upmc.edu.
Elizabeth HeadDepartment of Pathology and Laboratory Medicine, University of California, Irvine, CA, USA; Alzheimer's Disease Research Center, University of California, Irvine, CA, USA; University of California, Irvine Institute for Memory Impairments and Neurological Disorders, CA, USA; Alzheimer Biomarker Consortium-Down Syndrome, University of California, Irvine, CA, USA; Center for Aging Research in Down Syndrome, University of California, Irvine, CA, USA. Electronic address: heade@uci.edu.
Alzheimer Biomarkers Consortium - Down Syndrome (ABC-DS)

Funding

University of Pittsburgh Clinical and Translational Science InstituteUL1TR001857 · NCATS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI REIS, STEVEN E · 2016 to 2025
$129.3M
National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD)U24AG021886 · NIA · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI TATIANA M. FOROUD · 2002 to 2026
$119.8M
Project 3: Biomarkers for DS Clinical TrialsU19AG068054 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LEE, JOSEPH HYUNGWOO · 2020 to 2025
$103.7M
Clinical and Translational Science AwardUL1TR001873 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI REILLY, MUREDACH P · 2016 to 2025
$99.0M
WU INSTITUTE OF CLINICAL AND TRANSLATIONAL SCIENCESUL1TR002345 · NCATS · WASHINGTON UNIVERSITY · PI William G. Powderly · 2017 to 2026
$97.8M
University of Wisconsin Institute for Clinical and Translational ResearchUL1TR002373 · NCATS · UNIVERSITY OF WISCONSIN-MADISON · PI ELIZABETH S BURNSIDE, Allan R. Brasier · 2017 to 2026
$75.9M
Satellite Diagnostic and Treatment Clinic CoreP50AG008702 · NIA · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI DE JAGER, PHILIP L · 1989 to 2019
$46.3M
Research Education ComponentP30AG062421 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI Christine S Ritchie · 2019 to 2026
$36.5M
University of California Health Participation in the National COVID Cohort Collaborative (N3C)UL1TR001414 · NCATS · UNIVERSITY OF CALIFORNIA-IRVINE · PI COOPER, DAN M, VILAIN, ERIC J. · 2015 to 2023
$35.1M
Wisconsin Alzheimer's Disease Research CenterP30AG062715 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI Sanjay Asthana · 2019 to 2026
$34.5M
The Alzheimer's Disease Research Center at the University of California, IrvineP30AG066519 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI Mathew Mark Blurton-Jones · 2020 to 2026
$27.9M
Biomarkers of Alzheimer's Disease in Adults with Down SyndromeU01AG051412 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI LOTT, IRA T., SCHUPF, NICOLE · 2015 to 2019
$26.3M
NCATS NIH HHS UL1 TR001414NCATS NIH HHS UL1 TR001857NCATS NIH HHS UL1 TR001873NCATS NIH HHS UL1 TR002345NCATS NIH HHS UL1 TR002373NIA NIH HHS P30 AG062421NIA NIH HHS P30 AG062715NIA NIH HHS P30 AG066519NIA NIH HHS P30 AG072946NIA NIH HHS P50 AG008702NIA NIH HHS P50 AG016570NIA NIH HHS RF1 AG079519NIA NIH HHS U01 AG051406NIA NIH HHS U01 AG051412NIA NIH HHS U19 AG068054NIA NIH HHS U24 AG021886NICHD NIH HHS P50 HD105353NICHD NIH HHS R01 HD064993NICHD NIH HHS U54 HD087011NICHD NIH HHS U54 HD090256NINDS NIH HHS T32 NS121727
6 · The paper itself

Abstract

Aquaporin-4 (AQP4) is implicated in Alzheimer's disease (AD) pathology through its role in astrocytic function, cerebrovascular integrity, and beta-amyloid (Aβ) clearance. Impaired Aβ clearance in AD is linked to changes in AQP4 distribution; however, the role of AQP4 in AD associated with Down Syndrome (DS) is poorly understood. This study investigates AQP4 protein levels, its relationship with Aβ deposition, and distribution patterns in DS. Using human post-mortem brain sections from the frontal and occipital cortex, we analyzed AQP4 and Aβ levels in samples from neurotypical controls, DS, DS with AD (DSAD), and late onset AD (LOAD). Protein levels and distribution were assessed using immunohistochemistry and immunofluorescence with quantitative imaging tools. AQP4 protein levels were higher with age in both neurotypical control and DS groups, but not in the LOAD group. AQP4 and Aβ were positively correlated with age in the frontal cortex of all groups. AQP4 and Aβ were positively correlated with each other after adjusting for age in the frontal cortex in both the control and DS groups which was not observed in the occipital cortex. In the frontal cortex of both DS and DSAD, AQP4 was more frequently distributed to the soma and proximal branches and less to astrocytic endfeet compared to the control group, consistent with previous reports of impaired glymphatic clearance and perivascular regulation. These findings support a relationship between altered AQP4 protein levels and distribution, Aβ accumulation, and region-specific vulnerability in DS and AD.

Indexed as

AgingAlzheimer DiseaseAquaporin 4AstrocytesBrainDown SyndromeAdultAgedAged, 80 and overAmyloid beta-PeptidesFemaleFrontal LobeHumansMaleMiddle AgedOccipital LobeAmyloid beta-PeptidesAQP4 protein, humanAquaporin 4AgingAstrocytesbeta-amyloidGliaNeurodegenerationTrisomy 21

Identifiers

PMID40987419
PMCPMC13341133

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