{
  "abstract": "INTRODUCTIONBiomarkers for monitoring disease activity and treatment response in peripheral neuropathies remain limited. Big tau, a high-molecular-weight isoform of tau, is predominantly expressed in the peripheral nervous system (PNS). We investigated serum levels of big tau, brain-derived tau (BD-tau), and neurofilament light chain (NfL) in peripheral neuropathies, multiple sclerosis (MS), Alzheimers disease (AD), and healthy controls (HC).\n\nMETHODSUltra-sensitive blood-based assays run on an HD-X Single Molecule Array analyser (Quanterix) were used to measure big tau and BD-tau in serum from patients with Guillain-Barre syndrome (GBS, n=81), Miller Fisher syndrome (MFS, n=20), Charcot-Marie-Tooth disease (CMT, n=102), chronic inflammatory demyelinating polyneuropathy (CIDP, n=43), MS (n=159), AD (n=20), and HC (n=41). NfL was measured in patients with neuropathies using an SR-X Single Molecule Array analyser (Quanterix).\n\nRESULTSSerum big tau levels were higher in GBS than in AD (11.4 vs 2.4 pg/mL, p<0.0001) and MS (11.4 vs 9.0 pg/mL, p=0.01), and similar to CIDP and CMT. Contrarily, serum BD-tau levels in GBS were higher than in CIDP (3.0 vs 2.3 pg/mL, p=0.006) and MS (3.0 vs 1.7 pg/mL, p<0.0001), but similar to CMT, and lower than in AD (3.0 vs 9.8 pg/mL, p<0.0001). Serum NfL levels were higher in GBS than in CIDP (32.5 vs 13.0 pg/mL, p=0.0002), CMT (32.5 vs 12.3 pg/mL, p<0.0001), and HC (32.5 vs 7.6 pg/mL, p<0.0001). Compared with GBS, MFS patients showed higher BD-tau (12.7 vs 3.0 pg/mL, p=0.003), lower big tau (5.4 vs 11.4 pg/mL, p=0.002), and higher NfL levels, although the latter did not reach statistical significance (118.3 vs 32.5 pg/mL, p=0.16). The NfL/big tau ratio was significantly higher in MFS than in GBS, CIDP, and CMT. In GBS, BD-tau correlated with early clinical severity (MRC at 1 week; I-RODS at 4 weeks; maximum GBS-DS and GBS-DS at 4 weeks), whereas neither tau biomarker showed long-term clinical correlations. Higher BD-tau and big tau levels were associated with the need for mechanical ventilation (BD-tau: 8.6 vs 2.9 pg/mL, p=0.019; big tau: 19.7 vs 10.7 pg/mL, p=0.007), while higher BD-tau levels were associated with mortality (10.9 vs 2.9 pg/mL, p=0.003).\n\nCONCLUSIONSHigher big tau levels in peripheral neuropathies than in CNS diseases support its role as a PNS-specific biomarker. In MFS, increased serum BD-tau, reduced big tau, and an elevated NfL/big tau ratio suggest CNS involvement with relative preservation of the PNS.",
  "abstract_shown": true,
  "affiliations": [
    "Neurological Diseases, IR SANT PAU, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, 08041, Barcelona, Spain"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 32,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "L. Martin-Aguilar"
    },
    {
      "name": "F. Gonzalez-Ortiz"
    },
    {
      "name": "H. Zetterberg"
    },
    {
      "name": "T. K. Karikari"
    },
    {
      "name": "M. Suarez-Calvet"
    },
    {
      "name": "C. Casasnovas"
    },
    {
      "name": "G. Gutierrez-Gutierrez"
    },
    {
      "name": "M. J. Sedano-Tous"
    },
    {
      "name": "J. Pardo-Fernandez"
    },
    {
      "name": "C. Marquez-Infante"
    },
    {
      "name": "I. Rojas-Marcos"
    },
    {
      "name": "I. Jerico-Pascual"
    },
    {
      "name": "E. Martinez-Hernandez"
    },
    {
      "name": "G. Moris de la Tassa"
    },
    {
      "name": "C. Dominguez-Gonzalez"
    },
    {
      "name": "T. Sevilla"
    },
    {
      "name": "A. L. Pelayo"
    },
    {
      "name": "R. Rojas-Garcia"
    },
    {
      "name": "R. Collet-Vidiella"
    },
    {
      "name": "H. Codes-Mendez"
    },
    {
      "name": "M. Caballero-Avila"
    },
    {
      "name": "C. Tejada-Illa"
    },
    {
      "name": "C. Lleixa"
    },
    {
      "name": "G. Riesco-Navarro"
    },
    {
      "name": "N. Blanco-Sanroman"
    },
    {
      "name": "T. Mederer-Fernandez"
    },
    {
      "name": "L. Panicot-Buj"
    },
    {
      "name": "E. Pascual-Goni"
    },
    {
      "name": "A. Vidal-Jordana"
    },
    {
      "name": "K. Blennow"
    },
    {
      "name": "H. Kvartsberg"
    },
    {
      "name": "L. Querol"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/cm7n5vm8wkz1g.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.08.27.26361202",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.08.27.26361202v1.full",
  "id": "cm7n5vm8wkz1g",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.08.27.26361202v1",
  "language": null,
  "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": [
    [
      "medrxiv",
      "neurology"
    ],
    [
      "openalex",
      "2728|Peripheral Neuropathies and Disorders"
    ]
  ],
  "openalex": "W7204781596",
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.08.27.26361202v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-08-27",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/cm7n5vm8wkz1g.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:26Z",
      "native_id": "10.64898/2026.08.27.26361202",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.08.27.26361202v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "medrxiv:neurology",
      "subfield": "neurology"
    }
  ],
  "title": "Big tau and brain-derived tau reveal peripheral and central nervous system involvement in neuropathies",
  "title_text": "Big tau and brain-derived tau reveal peripheral and central nervous system involvement in neuropathies",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:26Z",
  "url": "https://research.draconitic.com/paper/cm7n5vm8wkz1g",
  "venue": "medRxiv",
  "versions": []
}