{
  "abstract": "TAR DNA-binding protein (TDP-43) cytoplasmic aggregates and nuclear depletion contribute to TDP-43 dysfunction in frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP) and forms of motor neuron disease (MND), particularly amyotrophic lateral sclerosis (ALS). TDP-43 regulates alternative splicing, but its dysfunction can engender the inclusion of cryptic exons (CEs) during splicing. Transcripts harboring an in-frame CE can generate de novo proteins. One example is the CE variant of hepatoma-derived growth factor-like protein 2 (HDGFL2-CE). To understand HDGFL2-CE as a readout of TDP-43 dysfunction, and its spatial relationship with TDP-43 pathology, we generate anti-HDGFL2-CE polyclonal and monoclonal antibodies and develop sensitive HDGFL2-CE immunoassays. With these tools, we observe that HDGFL2-CE accumulates in neurons with TDP-43 pathology, and that higher frontal cortex HDGFL2-CE in FTLD-TDP and FTLD-TDP/MND associates with greater pathological TDP-43, earlier age of onset, and shorter survival, supporting HDGFL2-CE as a marker tightly linked to TDP-43 dysfunction and clinical disease features.",
  "abstract_shown": true,
  "affiliations": [
    "Neuroscience Institute, University of Miami Miller School of Medicine, Miami, FL 33136, USA",
    "Department of Biochemistry & Molecular Biology, University of Miami, Miami, FL 33136, USA",
    "Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA",
    "Banner Sun Health Research Institute, Sun City, AZ 85351, USA",
    "Department of Neurology, Mayo Clinic, Jacksonville, FL 32224, USA",
    "Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA",
    "Department of Neurology, University of California, San Francisco, San Francisco, CA 91358, USA",
    "Banner Alzheimer’s Institute, University of Arizona, Phoenix, AZ 85006, USA",
    "Department of Neurology, University of Miami, Miami, FL 33136, USA"
  ],
  "article_type": "brief report",
  "arxiv": null,
  "author_total": 28,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Kathryn J. Citrano"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Vidhya Bharathi Maheswari Jawahar"
    },
    {
      "affs": [
        2
      ],
      "name": "Madison M. Reeves"
    },
    {
      "affs": [
        2
      ],
      "name": "Leonardo Petrucelli"
    },
    {
      "affs": [
        2
      ],
      "name": "Yari Carlomagno"
    },
    {
      "affs": [
        2
      ],
      "name": "Mei Yue"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Jorge Alaiz Noya"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Lillian M. Daughrity"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Raul Baena Tomé"
    },
    {
      "affs": [
        2
      ],
      "name": "Karen Jansen-West"
    },
    {
      "affs": [
        2
      ],
      "name": "Bailey Rawlinson"
    },
    {
      "affs": [
        2
      ],
      "name": "Michael DeTure"
    },
    {
      "affs": [
        2
      ],
      "name": "Erica Engelberg-Cook"
    },
    {
      "affs": [
        3
      ],
      "name": "Alpana Singh"
    },
    {
      "affs": [
        4
      ],
      "name": "Neill R. Graff-Radford"
    },
    {
      "affs": [
        4
      ],
      "name": "Gregory S. Day"
    },
    {
      "affs": [
        5
      ],
      "name": "Bradley F. Boeve"
    },
    {
      "affs": [
        6
      ],
      "name": "Adam L. Boxer"
    },
    {
      "affs": [
        5
      ],
      "name": "David S. Knopman"
    },
    {
      "affs": [
        5
      ],
      "name": "Keith A. Josephs"
    },
    {
      "affs": [
        5
      ],
      "name": "Ronald C. Petersen"
    },
    {
      "affs": [
        4
      ],
      "name": "Björn Oskarsson"
    },
    {
      "affs": [
        3,
        7
      ],
      "name": "Nicholas J. Ashton"
    },
    {
      "affs": [
        2
      ],
      "name": "Dennis W. Dickson"
    },
    {
      "affs": [
        0,
        2,
        8
      ],
      "name": "Tania F. Gendron"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Mercedes Prudencio"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Yong-Jie Zhang"
    },
    {
      "affs": [
        0,
        2,
        8
      ],
      "name": "Leonard Petrucelli"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/77emm81mr703f.bib",
  "cited_by": 0,
  "doi": "10.1016/j.xcrm.2026.103105",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13710691/",
  "id": "77emm81mr703f",
  "issns": [
    "2666-3791"
  ],
  "landing_url": "https://doi.org/10.1016/j.xcrm.2026.103105",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Report"
    ],
    [
      "openalex",
      "2728|Amyotrophic Lateral Sclerosis Research"
    ]
  ],
  "openalex": "W7221151737",
  "pdf_url": null,
  "pmcid": "PMC13710691",
  "pmid": "42854693",
  "published": "2026-10-09",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/77emm81mr703f.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:21:36Z",
      "native_id": "PMC13710691",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.xcrm.2026.103105"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2728|Amyotrophic Lateral Sclerosis Research",
      "subfield": "neurology"
    }
  ],
  "title": "Anti-HDGFL2 cryptic protein antibodies provide a sensitive readout of TDP-43 pathology and clinical disease features",
  "title_text": "Anti-HDGFL2 cryptic protein antibodies provide a sensitive readout of TDP-43 pathology and clinical disease features",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:21:36Z",
  "url": "https://research.draconitic.com/paper/77emm81mr703f",
  "venue": "Cell Reports Medicine",
  "versions": []
}