Evidence map›Paper›PMID 40133235›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025

Carbonic anhydrase inhibitors prevent presymptomatic capillary flow disturbances in a model of cerebral amyloidosis.

Eugenio Gutiérrez-Jiménez, Peter Mondrup Rasmussen, Irene Klærke Mikkelsen, Sreekanth Kura, Signe K Fruekilde, Brian Hansen, Luca Bordoni, Jasper Carlsen, Johan Palmfeldt, David A Boas and 11 more

Abstract read
In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Cerebral proteome adaptations to amyloid angiopathy are prevented by carbonic anhydrase inhibitors.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
  5. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors.

Eugenio Gutiérrez-JiménezCenter of Functionally Integrative Neuroscience, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.ORCID 0000-0002-7509-0720
Peter Mondrup RasmussenCenter of Functionally Integrative Neuroscience, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Irene Klærke MikkelsenCenter of Functionally Integrative Neuroscience, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Sreekanth KuraDepartment of Biomedical Engineering, Boston University, Boston, Massachusetts, USA.
Signe K FruekildeCenter of Functionally Integrative Neuroscience, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Brian HansenCenter of Functionally Integrative Neuroscience, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Luca BordoniGliaLab and Letten Centre, Division of Anatomy, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
Jasper CarlsenResearch Unit for Molecular Medicine (MMF), Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Johan PalmfeldtResearch Unit for Molecular Medicine (MMF), Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
David A BoasDepartment of Biomedical Engineering, Boston University, Boston, Massachusetts, USA.
Sava SakadžićAthinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.
Sergei VinogradovDepartment of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Mirna El KhatibDepartment of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Jaime Ramos-CejudoDepartment of Psychiatry and Neurology, New York University (NYU) Grossman School of Medicine, New York City, New York, USA.
Boris WiedCenter of Functionally Integrative Neuroscience, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Desiree Leduc-GalindoCenter of Functionally Integrative Neuroscience, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Elisa CanepaAlzheimer's Center at Temple, Department of Neural Sciences, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania, USA.
Adam C MarDepartment of Neuroscience and Physiology, Neuroscience Institute, New York University (NYU) Grossman School of Medicine, New York, New York, USA.
Begona Gamallo-LanaDepartment of Neuroscience and Physiology, Neuroscience Institute, New York University (NYU) Grossman School of Medicine, New York, New York, USA.
Silvia FossatiAlzheimer's Center at Temple, Department of Neural Sciences, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania, USA.
Leif ØstergaardCenter of Functionally Integrative Neuroscience, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.

Funding

Research Education ComponentP30AG066512 · NIA · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI Mary Sherman Mittelman · 2020 to 2026
$28.4M
Investigating the Microvascular Mechanisms of O2 Supply-Demand Mismatch in Small Vessel Disease using Novel High-Resolution Optical ImagingR01NS115401 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI AYATA, CENK, SAKADZIC, SAVA · 2020 to 2024
$3.5M
Potentiation of CAA-mediated endothelial dysfunction by cardiovascular risk factorsR01NS104127 · NINDS · TEMPLE UNIV OF THE COMMONWEALTH · PI FOSSATI, SILVIA · 2018 to 2022
$3.0M
Targeting carbonic anhydrases in Alzheimer's diseaseR01AG062572 · NIA · TEMPLE UNIV OF THE COMMONWEALTH · PI FOSSATI, SILVIA · 2019 to 2023
$2.3M
Oxygen imaging by phosphorescence quenchingU24EB028941 · NIBIB · UNIVERSITY OF PENNSYLVANIA · PI VINOGRADOV, SERGEI · 2019 to 2023
$1.6M
Two-photon Imaging of Oxygen and Blood Flow in Retinal and Cerebral VasculatureR01NS121095 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI Sava Sakadzic, Mahnaz Shahidi · 2024 to 2026
$1.3M
Alzheimer's Association AARF-18-564411Karen Toffler Charitable TrustLundbeck Foundation R310-2018-3455NIA NIH HHS P30 AG066512NIA NIH HHS R01 AG062572NIBIB NIH HHS U24 EB028941NIH HHS R01AG062572NIH HHS R01NS104127NIH USA U24EB028941NINDS NIH HHS R01 NS104127NINDS NIH HHS R01 NS115401NINDS NIH HHS R01 NS121095VELUX Foundation 0026167
6 · The paper itself

Abstract

introductionDisturbances in microvascular flow dynamics are hypothesized to precede the symptomatic phase of Alzheimer's disease (AD). However, evidence in presymptomatic AD remains elusive, underscoring the need for therapies targeting these early vascular changes.

methodsWe employed a multimodal approach, combining in vivo optical imaging, molecular techniques, and ex vivo magnetic resonance imaging, to investigate early capillary dysfunction in C57BL/6-Tg(Thy1-APPSwDutIowa)BWevn/Mmjax (Tg-SwDI) mice without memory impairment. We also assessed the efficacy of carbonic anhydrase inhibitors (CAIs) in preventing capillary flow disturbances.

resultsOur study revealed capillary flow disturbances associated with alterations in capillary morphology, adhesion molecule expression, and amyloid beta (Aβ) load in 9- to 10-month-old Tg-SwDI mice without memory impairment. CAI treatment ameliorated these capillary flow disturbances, enhanced oxygen availability, and reduced Aβ load. DISCUSSION: These findings underscore the importance of capillary flow disturbances as early biomarkers in presymptomatic AD and highlight the potential of CAIs for preserving vascular integrity in the early stages of AD. HIGHLIGHTS: Uncovered early capillary dysfunction in a presymptomatic Alzheimer's disease (AD) mouse model. Evidence linking capillary stalls and capillary dysfunction with oxygen delivery issues in AD. Novel use of carbonic anhydrase inhibitors to prevent early capillary flow disturbances in AD.

Indexed as

CapillariesCarbonic Anhydrase InhibitorsCerebral Amyloid AngiopathyCerebrovascular CirculationAlzheimer DiseaseAmyloid beta-PeptidesAnimalsBrainDisease Models, AnimalMagnetic Resonance ImagingMaleMiceMice, Inbred C57BLMice, TransgenicAmyloid beta-PeptidesCarbonic Anhydrase InhibitorsAlzheimer's diseasecapillary dysfunctioncapillary flow disturbancescapillary stallscarbonic anhydrase inhibitorspresymptomatic

Identifiers

PMID40133235
PMCPMC11936728

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Registered trials

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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.