{
  "abstract": "Molecular staging of Alzheimer's disease (AD) increasingly defines transition boundaries along single-cell pseudo-progression trajectories, yet whether such boundaries reproduce across brain regions, cohorts and molecular modalities is rarely tested. We present a permutation-controlled audit that combines nine boundary-detection algorithms with a fixed marker panel and four orthogonal reproducibility axes-algorithmic consensus, region, cohort and modality. On synthetic data with planted ground-truth boundaries the audit reaches 100% sensitivity and 94% specificity, rejecting four distinct artefact classes each by a different axis. Applied to the Seattle Alzheimer's Disease Brain Cell Atlas middle temporal gyrus, it localizes a transition that is robust across algorithms and recovered in most cell types but does not generalize: its leading marker is attenuated or absent in prefrontal cortex, entorhinal cortex and cerebrospinal fluid, and an apparent cross-region conservation of glial metabolic genes proves to be a global-expression offset rather than a shared program. The same audit nonetheless certifies an externally validated marker (astrocytic PTGDS) as reproducible across regions and modalities, showing that it separates generalizable anchors from dataset-specific ones rather than rejecting all signals. We provide this four-axis audit as a transferable, code-available standard to apply before a trajectory boundary is read as a biological stage, in AD and other progressive proteinopathies.",
  "abstract_shown": true,
  "affiliations": [
    "BIOXP"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Y. Kim"
    },
    {
      "name": "W. Heo"
    },
    {
      "name": "S. J. Park"
    },
    {
      "affs": [
        0
      ],
      "name": "Y. Kim"
    },
    {
      "name": "Y. E. Cho"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bn3wfr61bjv89.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.08.24.746808",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.08.24.746808v1.full",
  "id": "bn3wfr61bjv89",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.08.24.746808v1",
  "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",
      "1312|Single-cell and spatial transcriptomics"
    ]
  ],
  "openalex": "W7204884322",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.08.24.746808v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-08-24",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/bn3wfr61bjv89.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:49Z",
      "native_id": "10.64898/2026.08.24.746808",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.08.24.746808v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:neuroscience",
      "subfield": "neuroscience"
    }
  ],
  "title": "A reproducibility-audit framework for generalizable versus dataset-specific molecular transition boundaries in Alzheimer's disease",
  "title_text": "A reproducibility-audit framework for generalizable versus dataset-specific molecular transition boundaries in Alzheimer's disease",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:49Z",
  "url": "https://research.draconitic.com/paper/bn3wfr61bjv89",
  "venue": "bioRxiv",
  "versions": []
}