{
  "abstract": "ImportanceBlood biomarkers for Alzheimer disease(AD), Parkinson disease(PD), and amyotrophic lateral sclerosis(ALS) are typically developed as disease-specific single-analyte tests. Whether one shared plasma panel can support disease-selective classification remains unclear.\n\nObjectiveTo test whether the Olink Target 48 Neurodegeneration plasma panel, analyzed with disease-specific Elastic Net models, can discriminate AD, PD, and ALS in a heterogeneous neurological cohort.\n\nDesign, Setting, and ParticipantsSingle-center diagnostic cohort study at Keio University Hospital, Tokyo, Japan. After quality control and one consent withdrawal, 302 participants were analyzed(healthy controls n = 62; AD continuum n = 93; PD n = 39; ALS n = 27; other neurological disorders n = 81) and allocated by diagnosis-stratified sampling into a discovery training set(n = 211) and a locked hold-out test set(n = 91).\n\nExposuresPlasma normalized protein expression from 42 assays retained after protein quality control. Plasma DOPA decarboxylase was excluded a priori from all classifiers because blood levels primarily reflect dopaminergic treatment exposure.\n\nMain Outcomes and MeasuresHold-out receiver operating characteristic area under the curve(AUC). Sensitivity and specificity at a training-set Youden threshold locked for Test.\n\nResultsHold-out AUCs were 0.974(95% CI, 0.942-0.995) for AD, 0.926(0.820-1.000) for PD, and 0.995(0.980-1.000) for ALS. At locked Youden cutoffs, sensitivity was 0.929 (95% CI, 0.765-0.991) and specificity was 0.921 (95% CI, 0.824-0.974) for AD, 0.833 (95% CI, 0.516-0.979) and 0.975 (95% CI, 0.912-0.997) for PD, and 1.000 (95% CI, 0.631-1.000) and 0.940 (95% CI, 0.865-0.980) for ALS.\n\nConclusions and RelevanceA single plasma neurodegeneration panel supported disease-selective classification of AD, PD, and ALS in internal validation. Multicenter external validation is needed before clinical application.\n\nKey PointsO_ST_ABSQuestionC_ST_ABSCan a single plasma neurodegeneration panel classify Alzheimer disease (AD), Parkinson disease (PD), and amyotrophic lateral sclerosis (ALS) in a heterogeneous neurological cohort?\n\nFindingsIn this diagnostic cohort study, disease-specific Elastic Net models derived from a single plasma panel enabled the discrimination of AD, PD, and ALS from other neurological disorders and healthy controls.\n\nMeaningA single plasma neurodegeneration panel can simultaneously support disease-selective classification of AD, PD, and ALS, offering a unified approach to blood-based diagnosis.",
  "abstract_shown": true,
  "affiliations": [
    "Keio University School of Medicine, Keio Hospital"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 21,
  "authors": [
    {
      "name": "K. Okada"
    },
    {
      "name": "S. Shimohama"
    },
    {
      "name": "R. Okochi"
    },
    {
      "name": "S. Bun"
    },
    {
      "name": "K. Takahata"
    },
    {
      "name": "H. Tabuchi"
    },
    {
      "name": "Y. Iwabuchi"
    },
    {
      "name": "T. Tezuka"
    },
    {
      "name": "T. Nukariya"
    },
    {
      "name": "S. Okusa"
    },
    {
      "name": "Y. Nihei"
    },
    {
      "name": "S. Morimoto"
    },
    {
      "name": "S. Takahashi"
    },
    {
      "name": "K. Tai"
    },
    {
      "name": "Y. Sato"
    },
    {
      "name": "J. Kuromitsu"
    },
    {
      "name": "J. Nakahara"
    },
    {
      "name": "M. Seki"
    },
    {
      "name": "H. Okano"
    },
    {
      "name": "M. Mimura"
    },
    {
      "affs": [
        0
      ],
      "name": "D. Ito"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/86nrsg3z4vb0s.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.19.26365782",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.10.19.26365782v1.full",
  "id": "86nrsg3z4vb0s",
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  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.10.19.26365782v1",
  "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": [
    [
      "medrxiv",
      "neurology"
    ],
    [
      "openalex",
      "2738|Dementia and Cognitive Impairment Research"
    ]
  ],
  "openalex": "W7223119659",
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.10.19.26365782v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-19",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/86nrsg3z4vb0s.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:21:27Z",
      "native_id": "10.64898/2026.10.19.26365782",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.10.19.26365782v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "medrxiv:neurology",
      "subfield": "neurology"
    }
  ],
  "title": "Plasma Proteomic Classification of Alzheimer Disease, Parkinson Disease, and Amyotrophic Lateral Sclerosis Using a Single Neurodegeneration Panel: A Diagnostic Cohort Study",
  "title_text": "Plasma Proteomic Classification of Alzheimer Disease, Parkinson Disease, and Amyotrophic Lateral Sclerosis Using a Single Neurodegeneration Panel: A Diagnostic Cohort Study",
  "type": "preprint",
  "updated_at": "2026-10-30T12:21:27Z",
  "url": "https://research.draconitic.com/paper/86nrsg3z4vb0s",
  "venue": "medRxiv",
  "versions": []
}