Evidence map›Paper›PMID 42873864›Full record

ArticleScience advances2026

Mitochondrial carbonic anhydrase-VB inhibition rescues brain endothelial stress and memory in Alzheimer's disease models.

Nicole L Lemon, Elisa Canepa, Rafael Vázquez-Torres, Rebecca Parodi-Rullán, Tina Hirt, Lisa M Petersohn, Tashnuva Rifat, Maryam H Abyaneh, Marc A Ilies, Silvia Fossati

Abstract read
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In one paragraph

Article in Science advances, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

10 authors.

Nicole L LemonAlzheimer's Center at Temple, Department of Neural Sciences, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA.ORCID 0000-0002-5956-4666
Elisa CanepaAlzheimer's Center at Temple, Department of Neural Sciences, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA.ORCID 0000-0003-2906-7797
Rafael Vázquez-TorresAlzheimer's Center at Temple, Department of Neural Sciences, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA.
Rebecca Parodi-RullánAlzheimer's Center at Temple, Department of Neural Sciences, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA.ORCID 0000-0002-0466-1047
Tina HirtAlzheimer's Center at Temple, Department of Neural Sciences, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA.ORCID 0009-0003-9180-4628
Lisa M PetersohnDepartment of Pharmaceutical Sciences and Moulder Center for Drug Discovery Research, Temple University School of Pharmacy, Temple University, Philadelphia, PA, USA.ORCID 0009-0002-0507-6197
Tashnuva RifatDepartment of Pharmaceutical Sciences and Moulder Center for Drug Discovery Research, Temple University School of Pharmacy, Temple University, Philadelphia, PA, USA.ORCID 0009-0006-9497-3752
Maryam H AbyanehAlzheimer's Center at Temple, Department of Neural Sciences, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA.ORCID 0009-0008-8428-4595
Marc A IliesAlzheimer's Center at Temple, Department of Neural Sciences, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA.ORCID 0000-0003-0694-411X
Silvia FossatiAlzheimer's Center at Temple, Department of Neural Sciences, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA.ORCID 0000-0002-2047-222X

Funding

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
NIA NIH HHS R01 AG062572NINDS NIH HHS R01 NS104127
6 · The paper itself

Abstract

Alzheimer's disease (AD) is a devastating neurodegenerative disorder with no effective cure, characterized by the cerebral parenchymal and vascular accumulation of aggregated amyloid-β (Aβ) and hyperphosphorylated tau. Cerebrovascular and mitochondria dysfunction are early causal events in the progression of AD. Previous studies support that inhibiting carbonic anhydrases (CAs) may prevent mitochondrial and cerebrovascular dysfunction in AD models. Here, we selectively target the mitochondrial CA isoform CA-VB by pharmacological and genetic manipulation in human cerebral microvascular endothelial cells (hCMEC), and we confirm the protective effects of the CA-V inhibitor in AD mice. CA-V inhibition and CA-VB KO prevent Aβ induced mitochondria-mediated endothelial apoptosis, loss of barrier resistance, and hCMEC inflammatory activation. Strikingly, CA-V inhibition also mitigates caspase activation and endothelial cell activation in the brains of 3xTg AD mice, resulting in preserved memory function. Our results demonstrate that selective CA-V inhibition is an effective and promising strategy against AD-mediated cerebrovascular pathology, neuroinflammation and cognitive impairment.

Indexed as

Alzheimer DiseaseBrainCarbonic Anhydrase InhibitorsCarbonic AnhydrasesEndothelial CellsMemoryMitochondriaAmyloid beta-PeptidesAnimalsApoptosisDisease Models, AnimalHumansMiceMice, TransgenicAmyloid beta-PeptidesCarbonic Anhydrase InhibitorsCarbonic Anhydrases

Identifiers

PMID42873864
PMCPMC13665925

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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.