{ "abstract": "Background: Assessment of short-term within-subject variability and test-retest reliability of Alzheimer’s disease (AD)-related plasma biomarkers is important for real-world clinical implementation and interpretation in research studies. In this study we aimed to assess short-term variability and reliability of core AD plasma biomarkers, proposed ratios, and evaluate a broader proteomic panel.\n\nMethods: Two serial plasma samples were collected from each of the 92 participants enrolled in observational research studies over intervals ranging from 30 minutes to three months. Test-retest reliability and within-subject variability were assessed for 131 biomarkers measured on three immunoassays (Lumipulse G plasma p-tau217; Fujirebio, NULISAseq CNS Disease Panel and NULISAqpcr AD 5-Plex; Alamar Biosciences). We subsequently evaluated the stability of a dual cut-point approach for AD probability diagnostic categorisation and examined whether within-subject variability was associated with inter-sample interval (time between serial blood sampling).\n\nResults: All core AD plasma biomarkers assessed in this study (Aβ42, BD-p-tau181, BD-p-tau217, BD-p-tau231, p-tau181, p-tau217, p-tau231, GFAP and NfL) demonstrated strong correlations (r ≥ 0.79) and high reliability (ICC ≥ 0.84). Within-subject variability was moderate to low for core AD plasma biomarkers. Using a validated dual cut-point approach for plasma p-tau217, most individuals (92%) remained within the same diagnostic category (high/indeterminate/low) across both timepoints, and no individual moved across two boundaries (i.e. from high to low AD probability categorisation or vice versa). For the majority of analytes, within-subject variability was not associated with inter-sample interval after adjustment for age and sex, however, the core AD plasma biomarker, NfL did have a significant association.\n\nConclusions: While core AD plasma biomarkers had limited variability and high reliability over short-intervals, other central nervous system (CNS)-relevant biomarkers showed greater variability, which may be relevant for interpretation in association studies and clinical applications.\n\nSupplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s13195-026-02180-8.", "abstract_shown": true, "affiliations": [ "Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, WC1N 3AR UK", "UK Dementia Research Institute at UCL, University College London, London, UK", "Neurology Department, Royal Adelaide Hospital and Queen Elizabeth Hospital, Adelaide, Australia", "School of Medicine, Adelaide University, Adelaide, Australia", "Neuroimmunology & CSF Laboratory, National Hospital for Neurology and Neurosurgery, Queen Square, London, UK", "Department of Neuroinflammation, UCL Queen Square Institute of Neurology, London, UK", "MRC Centre for Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK", "Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden", "Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden", "Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI USA", "Wisconsin Alzheimer’s Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI USA", "Centre for Brain Research, Indian Institute of Science, Bangalore, India" ], "article_type": "research article", "arxiv": null, "author_total": 13, "authors": [ { "affs": [ 0, 1 ], "name": "Millie Beament" }, { "affs": [ 0, 1 ], "name": "Katharine Wiltshire" }, { "affs": [ 0, 2, 3 ], "name": "Christopher R S Belder" }, { "affs": [ 0, 1 ], "name": "Emily Abel" }, { "affs": [ 4, 5 ], "name": "Melanie Hart" }, { "affs": [ 1 ], "name": "Amanda J Heslegrave" }, { "affs": [ 4, 6 ], "name": "Michael P Lunn" }, { "affs": [ 0 ], "name": "Miguel Rosa-Grilo" }, { "affs": [ 1 ], "name": "Owen Swann" }, { "affs": [ 0, 1 ], "name": "Jonathan M Schott" }, { "affs": [ 1, 7, 8, 9, 10, 11 ], "name": "Henrik Zetterberg" }, { "affs": [ 0, 1 ], "name": "Nick C Fox" }, { "affs": [ 0, 1 ], "name": "Ashvini Keshavan" } ], "bibtex": "https://research.draconitic.com/paper/1dc94xej0dpq4.bib", "cited_by": 0, "doi": "10.1186/s13195-026-02180-8", "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13711881/", "id": "1dc94xej0dpq4", "issns": [ "1758-9193" ], "landing_url": "https://doi.org/10.1186/s13195-026-02180-8", "language": "en", "licence": "CC-BY-4.0", "licence_label": "CC BY 4.0", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "heading", "Research" ], [ "openalex", "2738|Dementia and Cognitive Impairment Research" ] ], "openalex": "W7223785278", "pdf_url": "https://link.springer.com/content/pdf/10.1186/s13195-026-02180-8.pdf", "pmcid": "PMC13711881", "pmid": "42947225", "published": "2026-10-27", "publisher": "BMC", "ris": "https://research.draconitic.com/paper/1dc94xej0dpq4.ris", "sources": [ { "first_seen": "2026-10-31T12:22:35Z", "native_id": "PMC13711881", "source": "pmc", "url": "https://doi.org/10.1186/s13195-026-02180-8" } ], "subjects": [ { "field": "medicine", "origin": "openalex:2738|Dementia and Cognitive Impairment Research", "subfield": "psychiatry" } ], "title": "Short-interval variability and test-retest reliability of Alzheimer’s disease plasma biomarkers in a clinically heterogenous cohort", "title_text": "Short-interval variability and test-retest reliability of Alzheimer’s disease plasma biomarkers in a clinically heterogenous cohort", "type": "peer-reviewed", "updated_at": "2026-10-31T12:22:35Z", "url": "https://research.draconitic.com/paper/1dc94xej0dpq4", "venue": "Alzheimer's Research & Therapy", "versions": [] }