{
  "abstract": "Alzheimer disease is characterized by extracellular amyloid-β deposition that contributes to neuronal dysfunction and degeneration. Although anti-amyloid-β antibodies reduce plaque burden, their use requires monitoring for amyloid-related imaging abnormalities. Here, phage display against immobilized Aβ40 fibrils representing a patient-relevant polymorph identified J8, a fibril-selective, Fc-free single-domain antibody. J8 bound fibrils with high apparent affinity, showed no detectable binding to monomeric Aβ40, decorated fibril surfaces, and recognized plaque-associated amyloid in Alzheimer disease brain tissue. During concurrent fibril exposure, J8 reduced apoptotic signaling in human induced pluripotent stem cell (iPSC)-derived cortical neurons and forebrain organoids. Single-nucleus profiling of pooled organoids identified fibril-associated stress programs and opposite-direction expression patterns in the FibJ8 condition; fibril-associated changes showed the strongest directional concordance with advanced disease pathology. These findings identify J8 as a fibril-selective candidate and support organoid-based evaluation of anti-amyloid reagents as a fit-for-purpose preclinical tool.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "Article",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "name": "Matt A. Greenlee"
    },
    {
      "name": "Soukaina Amniouel"
    },
    {
      "name": "Isabel Rivera"
    },
    {
      "name": "Jessica Suh"
    },
    {
      "name": "Natalia J. Martinez"
    },
    {
      "name": "Anton Simeonov"
    },
    {
      "name": "Elizabeth Head"
    },
    {
      "name": "Robert Tycko"
    },
    {
      "name": "Wei Zheng"
    },
    {
      "name": "Bryan D. Fleming"
    },
    {
      "name": "Qi Zhang",
      "orcid": "0000-0002-2639-9158"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ezqd5wtxnjyjb.bib",
  "cited_by": 0,
  "doi": "10.1016/j.isci.2026.117946",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13718768/?tool=EBI",
  "id": "ezqd5wtxnjyjb",
  "issns": [
    "2589-0042"
  ],
  "landing_url": "https://www.cell.com/iscience/fulltext/S2589-0042(26)03329-8",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "http://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "heading",
      "Cell biology"
    ],
    [
      "heading",
      "Neuroscience"
    ],
    [
      "openalex",
      "2737|Alzheimer's disease research and treatments"
    ]
  ],
  "openalex": "W7223093285",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13718768/pdf/?tool=EBI",
  "pmcid": "PMC13718768",
  "pmid": "42960253",
  "published": "2026-10-21",
  "publisher": "Elsevier BV",
  "ris": "https://research.draconitic.com/paper/ezqd5wtxnjyjb.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:16Z",
      "native_id": "10.1016/j.isci.2026.117946",
      "source": "feed-cell",
      "url": "https://www.cell.com/iscience/fulltext/S2589-0042(26)03329-8"
    },
    {
      "first_seen": "2026-10-30T12:17:49Z",
      "native_id": "10.1016/j.isci.2026.117946",
      "source": "crossref",
      "url": "https://linkinghub.elsevier.com/retrieve/pii/S2589004226033298"
    },
    {
      "first_seen": "2026-10-31T00:20:38Z",
      "native_id": "PMC:PMC13718768",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13718768"
    },
    {
      "first_seen": "2026-11-01T00:20:50Z",
      "native_id": "MED:42960253",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42960253"
    },
    {
      "first_seen": "2026-11-02T12:22:44Z",
      "native_id": "PMC13718768",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.isci.2026.117946"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "heading:Cell biology",
      "subfield": "cell-biology"
    },
    {
      "field": "biology",
      "origin": "heading:Neuroscience",
      "subfield": "neuroscience"
    }
  ],
  "title": "A fibril-selective single-domain antibody targets pathogenic amyloid-β assemblies and protects human neurons",
  "title_text": "A fibril-selective single-domain antibody targets pathogenic amyloid-β assemblies and protects human neurons",
  "type": "peer-reviewed",
  "updated_at": "2026-11-02T12:22:44Z",
  "url": "https://research.draconitic.com/paper/ezqd5wtxnjyjb",
  "venue": "iScience",
  "versions": []
}