{
  "abstract": "FDA-approved carbonic anhydrase inhibitors (CAIs) have shown robust efficacy in reducing amyloid- beta pathology, neurodegeneration, and cerebrovascular dysfunction in Alzheimer disease (AD) and cerebral amyloid angiopathy (CAA) models, highlighting carbonic anhydrases (CAs) as a promising, previously untapped therapeutic target for AD and the vascular contribution to dementia. We have recently shown that amyloid- beta aggregates disrupt neuro-signaling and deplete neurotrophic factors (particularly BDNF) in the heart of AD mouse models and human subjects. In this study, we present the first in-depth examination of CAI therapy (acetazolamide, ATZ) in Tg2576 mice, a well-established model of AD and CAA. We confirm that progressive cardiac fibrosis and amyloid- beta deposition in 13-month-old mice severely impair the cardiac neuro-signaling system, marked by a drastic decrease in BDNF and reductions in adrenergic fibers and regenerating nerve endings (TH and GAP-43 markers), leading to significant declines in ejection fraction and fractional shortening compared to age-matched WT littermates. Critically, this study demonstrates that long-term ATZ treatment in Tg2576 mice significantly reduces cardiac amyloid- beta burden, prevents adverse neuro-signaling remodeling, and restores heart physiological function, as assessed via speckle tracking strain echocardiography. These in vivo findings were corroborated in human cardiomyocytes, in which CA inhibition reduced human amyloid- beta40 oligomer-dependent disruption of CREB signaling, thus preserving BDNF expression. Together, these results reveal a previously unrecognized cardio-neuroprotective role for CAIs in preventing amyloid- beta-induced cardiovascular remodeling and neuro-signaling disruption in the Tg2576-AD model. Given the established benefits of CAIs on cerebrovascular function and cognition, our findings further support advancing repurposing efforts into clinical trials. CAIs such as ATZ could offer a dual-action therapy approach, addressing both the central nervous system and cardiac pathologies associated with AD and, potentially, the systemic effects of amyloidosis.",
  "abstract_shown": true,
  "affiliations": [
    "Temple University Lewis Katz School of Medicine"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "name": "A. Elia"
    },
    {
      "name": "R. Vazquez-Torres"
    },
    {
      "name": "A. Carey"
    },
    {
      "name": "M. Wolf"
    },
    {
      "name": "V. R. Gade"
    },
    {
      "name": "M. Alves"
    },
    {
      "affs": [
        0
      ],
      "name": "S. Fossati"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dy1h19zgb5j3b.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.08.757731",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.08.757731v1.full",
  "id": "dy1h19zgb5j3b",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.08.757731v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "cell biology"
    ],
    [
      "openalex",
      "2737|Alzheimer's disease research and treatments"
    ]
  ],
  "openalex": "W7221120444",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.08.757731v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-08",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/dy1h19zgb5j3b.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:26:48Z",
      "native_id": "10.64898/2026.10.08.757731",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.08.757731v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:cell biology",
      "subfield": "cell-biology"
    }
  ],
  "title": "Carbonic anhydrase inhibition rescues heart function in the Tg2576 Alzheimer's mouse model by ameliorating cardiac amyloid-β pathology and neurotrophic signaling impairment.",
  "title_text": "Carbonic anhydrase inhibition rescues heart function in the Tg2576 Alzheimer's mouse model by ameliorating cardiac amyloid-β pathology and neurotrophic signaling impairment.",
  "type": "preprint",
  "updated_at": "2026-10-30T12:26:48Z",
  "url": "https://research.draconitic.com/paper/dy1h19zgb5j3b",
  "venue": "bioRxiv",
  "versions": []
}