{
  "abstract": "Frontotemporal lobar degeneration (FTLD), predominantly comprised of tau and TDP-43 proteinopathies, is a common cause of early-onset dementia. Biomarkers that reliably classify FTLD subtypes are limited, thereby hindering in-vivo diagnosis and clinical trial stratification. We conducted large-scale, multi-platform cerebrospinal fluid proteomics in 566 individuals, including 274 FTLD-spectrum (48 autopsy-confirmed FTLD-TDP, 90 autopsy-confirmed FTLD-tau), 171 Alzheimers disease, and 95 controls. In neuropathological subtype contrasts, elevated matrix metalloproteinase MMP10 classified Picks disease (PiD) versus other subtypes with near-perfect accuracy across proteomic platforms. We further validated CSF MMP10 as a potential PiD diagnostic biomarker via a targeted immunoassay in an independent, autopsy-confirmed FTLD cohort. Post-synaptic proteins HOMER1 and DLG4 exhibited elevations across FTLD-TDP subtypes (A, B, and C) versus FTLD-tau. Network analysis identified RNA metabolism and pro-inflammatory signatures in FTLD-TDP, and cytoskeletal and heat shock signatures in progressive supranuclear palsy. These findings reveal candidate diagnostic biomarkers and proteomic pathways underlying FTLD clinico-pathological heterogeneity.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 35,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "R. Saloner"
    },
    {
      "name": "L. Cornelis"
    },
    {
      "name": "J. Downer"
    },
    {
      "name": "C. Dietz"
    },
    {
      "name": "B. Chan"
    },
    {
      "name": "M. Hughes"
    },
    {
      "name": "M. Olzinski"
    },
    {
      "name": "Y. Cobigo"
    },
    {
      "name": "A. Lario-Lago"
    },
    {
      "name": "H. Heuer"
    },
    {
      "name": "K. Cody"
    },
    {
      "name": "M. Wood"
    },
    {
      "name": "K. A. Q. Cousins"
    },
    {
      "name": "D. Wolk"
    },
    {
      "name": "E. B. Lee"
    },
    {
      "name": "D. Irwin"
    },
    {
      "name": "A. Abdelhak"
    },
    {
      "name": "B. F. Boeve"
    },
    {
      "name": "G. D. Rabinovici"
    },
    {
      "name": "R. La Joie"
    },
    {
      "name": "L. T. Grinberg"
    },
    {
      "name": "S. Spina"
    },
    {
      "name": "E. W. Paolillo"
    },
    {
      "name": "A. Staffaroni"
    },
    {
      "name": "L. VandeVrede"
    },
    {
      "name": "P. A. Ljubenkov"
    },
    {
      "name": "M. L. Gorno-Tempini"
    },
    {
      "name": "H. J. Rosen"
    },
    {
      "name": "J. S. Yokoyama"
    },
    {
      "name": "J. H. Kramer"
    },
    {
      "name": "K. B. Casaletto"
    },
    {
      "name": "B. Miller"
    },
    {
      "name": "W. W. Seeley"
    },
    {
      "name": "J. C. Rojas"
    },
    {
      "name": "A. L. Boxer"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7dy73th80fb00.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.29.755483",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.29.755483v1.full",
  "id": "7dy73th80fb00",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.29.755483v1",
  "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",
      "neuroscience"
    ],
    [
      "openalex",
      "2738|Dementia and Cognitive Impairment Research"
    ]
  ],
  "openalex": "W7220430484",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.29.755483v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-29",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/7dy73th80fb00.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:26:39Z",
      "native_id": "10.64898/2026.09.29.755483",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.29.755483v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:neuroscience",
      "subfield": "neuroscience"
    }
  ],
  "title": "Large-scale cerebrospinal fluid proteomics identifies diagnostic biomarker candidates across the clinico-pathological continuum of frontotemporal lobar degeneration",
  "title_text": "Large-scale cerebrospinal fluid proteomics identifies diagnostic biomarker candidates across the clinico-pathological continuum of frontotemporal lobar degeneration",
  "type": "preprint",
  "updated_at": "2026-10-30T12:26:39Z",
  "url": "https://research.draconitic.com/paper/7dy73th80fb00",
  "venue": "bioRxiv",
  "versions": []
}