{
  "abstract": "Background: To establish age-stratified plasma neurofilament light chain (NfL) reference intervals using a domestic Digital Single-Molecule Sensing (DiSMS) platform and to explore neuropathological profiles across amyotrophic lateral sclerosis (ALS), inflammatory demyelinating diseases (IDD) and healthy individuals.\n\nMethods: We enrolled 719 participants (510 healthy controls, 121 ALS, 88 IDD). Age-specific reference intervals defining the healthy boundary were established using the 2.5th–97.5th percentile method. Pathological separation utility was evaluated via age-stratified subgroup comparisons and receiver operating characteristic (ROC) analysis.\n\nResults: Plasma NfL levels in healthy individuals increased significantly with age (p<0.0001), with reference intervals of 2.68–17.09 pg/mL (20–49 years), 7.14–61.95 pg/mL (50–69 years) and 14.20–104.71 pg/mL (≥70 years). Out-of-boundary NfL elevation rates demonstrated prominent age-dependent fluctuations. In ALS, out-of-boundary elevation rates were 98.3% (57/58) for the 20–49 age group, 68.4% (39/57) for the 50–69 group and 50.0% (3/6) for the ≥70 group, capturing the aggressive tempo of primary motor neuron degeneration. In IDD—which primarily comprised patients in early, clinically stable phases—out-of-boundary rates were 17.0% (8/47) in the 20–49 group and 2.6% (1/38) in the 50–69 group. Age-stratified ROC analysis demonstrated exceptional separation capacity for ALS against healthy controls (area under the curve (AUC): 20–49 years=0.999; 50–69 years=0.964; ≥70 years=0.981) and against IDD (AUC: 20–49 years=0.910; 50–69 years=0.976). Intriguingly, in the 20–49 group where physiological ageing noise was minimal, the platform retained a modest capability to distinguish stable IDD from healthy controls (AUC=0.607).\n\nConclusion: Age-stratified plasma NfL mapping provides a rigorous normative framework for defining population-specific healthy boundaries in China. Rather than functioning as a standalone differential classifier, the dramatic cross-sectional variance in peripheral NfL magnitude successfully maps the distinct pathological spaces separating primary, continuous neurodegeneration (ALS) from quiescent neuroinflammation (IDD) across the adult lifespan, validating the analytical utility of domestic DiSMS platforms.",
  "abstract_shown": true,
  "affiliations": [
    "Tianjin Hospital, Tianjin, China",
    "Tianjin KingMed Diagnostics Laboratory Co. Ltd, Tianjin, China",
    "Tianjin Key Laboratory of Multi-omics Precision Diagnosis Technology for Neurological Diseases, Tianjin, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Jin Huang"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Haiyan Li"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Hailan Zhou"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Tong Li"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Jia Li"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Dequan Liu"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Keqiang Yan",
      "orcid": "0000-0002-9593-5284"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1c91gpenwxd9r.bib",
  "cited_by": 0,
  "doi": "10.1136/bmjno-2026-001715",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13735380/",
  "id": "1c91gpenwxd9r",
  "issns": [
    "2632-6140"
  ],
  "landing_url": "https://doi.org/10.1136/bmjno-2026-001715",
  "language": "en",
  "licence": "CC-BY-NC-4.0",
  "licence_label": "CC BY-NC 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "1506"
    ],
    [
      "heading",
      "Original Research"
    ],
    [
      "openalex",
      "2728|Amyotrophic Lateral Sclerosis Research"
    ]
  ],
  "openalex": "W7225094404",
  "pdf_url": "https://neurologyopen.bmj.com/content/8/2/e001715.full.pdf",
  "pmcid": "PMC13735380",
  "pmid": "42990777",
  "published": "2026-11-02",
  "publisher": "BMJ Publishing Group",
  "ris": "https://research.draconitic.com/paper/1c91gpenwxd9r.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T12:21:04Z",
      "native_id": "PMC13735380",
      "source": "pmc",
      "url": "https://doi.org/10.1136/bmjno-2026-001715"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2728|Amyotrophic Lateral Sclerosis Research",
      "subfield": "neurology"
    }
  ],
  "title": "Pathological separation utility of plasma neurofilament light chain (NfL) detected by a single-molecule immunoassay platform in neurodegenerative diseases",
  "title_text": "Pathological separation utility of plasma neurofilament light chain (NfL) detected by a single-molecule immunoassay platform in neurodegenerative diseases",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:21:04Z",
  "url": "https://research.draconitic.com/paper/1c91gpenwxd9r",
  "venue": "BMJ Neurology Open",
  "versions": []
}