{
  "abstract": "Scalable and accessible biomarkers of neurofibrillary tangle pathology are needed for Alzheimers disease prognosis, diagnosis and monitoring. Here, we show that a blood-based immunoassay for an endogenously-cleaved \"eMTBR-tau\" fragment of tau protein is strongly associated with autopsy-diagnosed Alzheimer neuropathologic change (ADNC) and predominantly reflects the burden and anatomical progression of tangle pathology but not amyloid plaque load despite being most elevated in amyloid-positive symptomatic individuals. Plasma eMTBR-tau was significantly more accurate than plasma p-tau217 in classifying Braak staging and ADNC statuses at autopsy. Importantly, neuropathologic classification by plasma eMTBR-tau remained high (AUC=0.91-0.95) even when increasing intervals between blood collection and death up to a decade, while maintaining superior sensitivity and specificity over p-tau217. Higher baseline plasma eMTBR-tau was associated with worse cognition cross-sectionally and longitudinally predicted faster worsening. These results were replicated in a living cohort with in vivo tangle and plaque neuroimaging. Plasma eMTBR-tau concordance with tau neuroimaging was up to 94%, suggesting surrogacy. Together, plasma eMTBR-tau captures biological signatures of Braak staging and ADNC over a prolonged pre-mortem window, highlighting potential for early disease detection, biological staging, prognosis and therapeutic development.",
  "abstract_shown": true,
  "affiliations": [
    "University of Pittsburgh"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "name": "R. Shi"
    },
    {
      "name": "X. Zeng"
    },
    {
      "name": "M. F. Farinas"
    },
    {
      "name": "M. N. Nafash"
    },
    {
      "name": "D. S. Smirnov"
    },
    {
      "name": "M. I. Kamboh"
    },
    {
      "name": "B. Snitz"
    },
    {
      "name": "J. K. Kofler"
    },
    {
      "name": "A. D. Cohen"
    },
    {
      "name": "T. A. Pascoal"
    },
    {
      "name": "M. D. Ikonomovic"
    },
    {
      "name": "H. Zetterberg"
    },
    {
      "name": "O. Lopez"
    },
    {
      "affs": [
        0
      ],
      "name": "T. K. Karikari"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ep9sw865tqns8.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.29.26363951",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.09.29.26363951v1.full",
  "id": "ep9sw865tqns8",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.09.29.26363951v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "medrxiv",
      "neurology"
    ],
    [
      "openalex",
      "2737|Alzheimer's disease research and treatments"
    ]
  ],
  "openalex": "W7220467007",
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.09.29.26363951v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-29",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/ep9sw865tqns8.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:07Z",
      "native_id": "10.64898/2026.09.29.26363951",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.09.29.26363951v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "medrxiv:neurology",
      "subfield": "neurology"
    }
  ],
  "title": "Plasma eMTBR-tau as a robust biomarker for Alzheimer's disease tangle pathology up to 10 years before death",
  "title_text": "Plasma eMTBR-tau as a robust biomarker for Alzheimer's disease tangle pathology up to 10 years before death",
  "type": "preprint",
  "updated_at": "2026-10-30T12:20:07Z",
  "url": "https://research.draconitic.com/paper/ep9sw865tqns8",
  "venue": "medRxiv",
  "versions": []
}