{
  "abstract": "Introduction\n\nThe growing number of assay platforms measuring blood-based biomarkers (BBMs) for Alzheimer's disease (AD) has introduced challenges in interpretability and comparability across assays. Differences across studies also limit comparability of data. To address these challenges, a systematic evaluation of harmonization methods is needed to support BBM data integration within or across studies.Methods\n\nTwo multisite studies, Alzheimer's Disease Neuroimaging Initiative (ADNI, n = 219) and Human Connectome Project (HCP, n = 111), were used to evaluate harmonization methods for mitigating assay and cohort effects in plasma phosphorylated tau 217 (p-tau217) measurements. Methods included various normalization, regression, and standardization approaches, including the recently developed CentiMarker. Assay effects were evaluated using repeated-measures data across assay platforms within each cohort, whereas cohort effects were assessed using pooled ADNI and HCP data. Harmonization performance was evaluated using distributional statistics and downstream modeling of p-tau217.Results\n\nQuantile normalization and quantile mapping methods were most effective for mitigating assay effects, whereas conditional quantile mapping performed best for pooled multi-cohort data. These methods also preserved biological variability. In contrast, simple means adjustment and reference-based Z-score standardization were least effective for mitigating assay effects, whereas simple means adjustment, Z-score standardization, and quantile normalization were least effective for mitigating cohort effects. CentiMarker had minimal impact on assay or cohort effects.Discussion\n\nBased on our evaluation, we recommend (conditional) quantile mapping for p-tau217 studies integrating data across multiple assays or cohorts. In contrast, we caution against using CentiMarker and Z-score-based methods, as they limit comparability and do not effectively mitigate technical variability.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Biostatistics and Health Data Science University of Pittsburgh School of Public Health Pittsburgh Pennsylvania USA.",
    "Department of Psychiatry University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA.",
    "Department of Radiology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA.",
    "Department of Neurology University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA.",
    "Alzheimer's Disease Research Center University of Pittsburgh Pittsburgh Pennsylvania USA."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Vivian Z Zhang"
    },
    {
      "affs": [
        1
      ],
      "name": "Pamela C L Ferreira"
    },
    {
      "affs": [
        0
      ],
      "name": "Yiwen Dong"
    },
    {
      "affs": [
        2
      ],
      "name": "Davneet Minhas"
    },
    {
      "affs": [
        1
      ],
      "name": "Guilherme Povala"
    },
    {
      "affs": [
        1
      ],
      "name": "Bruna Bellaver"
    },
    {
      "name": "Alzheimer's Disease Neuroimaging Initiative"
    },
    {
      "affs": [
        1,
        3,
        4
      ],
      "name": "Tharick A Pascoal"
    },
    {
      "affs": [
        1,
        4
      ],
      "name": "Xuemei Zeng"
    },
    {
      "affs": [
        1,
        4
      ],
      "name": "Thomas K Karikari"
    },
    {
      "affs": [
        1,
        4
      ],
      "name": "Ann D Cohen"
    },
    {
      "affs": [
        0,
        4
      ],
      "name": "Rebecca A Deek"
    },
    {
      "affs": [
        0
      ],
      "name": "Qiong Wu"
    },
    {
      "affs": [
        0,
        1,
        4
      ],
      "name": "Dana L Tudorascu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bjeky2aprctdg.bib",
  "cited_by": 0,
  "doi": "10.1002/dad2.70518",
  "fulltext_url": "https://europepmc.org/articles/PMC13691630",
  "id": "bjeky2aprctdg",
  "issns": [
    "2352-8729"
  ],
  "landing_url": "https://europepmc.org/article/MED/42921107",
  "language": "eng",
  "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": [
    [
      "openalex",
      "2738|Dementia and Cognitive Impairment Research"
    ]
  ],
  "openalex": "W7223375602",
  "pdf_url": "https://europepmc.org/articles/PMC13691630?pdf=render",
  "pmcid": "PMC13691630",
  "pmid": "42921107",
  "published": "2026-10-23",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/bjeky2aprctdg.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:33Z",
      "native_id": "MED:42921107",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42921107"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2738|Dementia and Cognitive Impairment Research",
      "subfield": "psychiatry"
    }
  ],
  "title": "Evaluation of harmonization methods to mitigate assay and cohort effects in plasma p-tau217.",
  "title_text": "Evaluation of harmonization methods to mitigate assay and cohort effects in plasma p-tau217.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:33Z",
  "url": "https://research.draconitic.com/paper/bjeky2aprctdg",
  "venue": "Alzheimer's & dementia (Amsterdam, Netherlands)",
  "versions": []
}