{
  "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.",
  "abstract_shown": true,
  "affiliations": [
    "Alzheimer’s Center at Temple, Department of Neural Sciences, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA.",
    "Department of Pharmaceutical Sciences and Moulder Center for Drug Discovery Research, Temple University School of Pharmacy, Temple University, Philadelphia, PA, USA."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Nicole L. Lemon",
      "orcid": "0000-0002-5956-4666"
    },
    {
      "affs": [
        0
      ],
      "name": "Elisa Canepa",
      "orcid": "0000-0003-2906-7797"
    },
    {
      "affs": [
        0
      ],
      "name": "Rafael Vázquez-Torres"
    },
    {
      "affs": [
        0
      ],
      "name": "Rebecca Parodi-Rullán",
      "orcid": "0000-0002-0466-1047"
    },
    {
      "affs": [
        0
      ],
      "name": "Tina Hirt",
      "orcid": "0009-0003-9180-4628"
    },
    {
      "affs": [
        1
      ],
      "name": "Lisa M. Petersohn",
      "orcid": "0009-0002-0507-6197"
    },
    {
      "affs": [
        1
      ],
      "name": "Tashnuva Rifat",
      "orcid": "0009-0006-9497-3752"
    },
    {
      "affs": [
        0
      ],
      "name": "Maryam H. Abyaneh",
      "orcid": "0009-0008-8428-4595"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Marc A. Ilies",
      "orcid": "0000-0003-0694-411X"
    },
    {
      "affs": [
        0
      ],
      "name": "Silvia Fossati",
      "orcid": "0000-0002-2047-222X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0svycdq5gwagv.bib",
  "cited_by": 0,
  "doi": "10.1126/sciadv.ady1161",
  "fulltext_url": "https://europepmc.org/articles/PMC13665925",
  "id": "0svycdq5gwagv",
  "issns": [
    "2375-2548"
  ],
  "landing_url": "https://www.science.org/doi/10.1126/sciadv.ady1161",
  "language": "eng",
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2737|Alzheimer's disease research and treatments"
    ]
  ],
  "openalex": "W7221754508",
  "pdf_url": "https://europepmc.org/articles/PMC13665925?pdf=render",
  "pmcid": "PMC13665925",
  "pmid": "42873864",
  "published": "2026-10-14",
  "publisher": "American Association for the Advancement of Science (AAAS)",
  "ris": "https://research.draconitic.com/paper/0svycdq5gwagv.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:41Z",
      "native_id": "10.1126/sciadv.ady1161",
      "source": "crossref",
      "url": "https://www.science.org/doi/10.1126/sciadv.ady1161"
    },
    {
      "first_seen": "2026-10-30T12:18:46Z",
      "native_id": "MED:42873864",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42873864"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2737|Alzheimer's disease research and treatments",
      "subfield": "physiology"
    }
  ],
  "title": "Mitochondrial carbonic anhydrase–VB inhibition rescues brain endothelial stress and memory in Alzheimer’s disease models",
  "title_text": "Mitochondrial carbonic anhydrase–VB inhibition rescues brain endothelial stress and memory in Alzheimer’s disease models",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:46Z",
  "url": "https://research.draconitic.com/paper/0svycdq5gwagv",
  "venue": "Science Advances",
  "versions": []
}