Biomarker Variability Limits Individualized Amyloid Time Estimation in Alzheimer Disease
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Le résumé fourni par la source
Objective: Disease progression modeling (DPM) or "amyloid time" is increasingly used to stage Alzheimer disease (AD). DPM performance depends on within-individual heterogeneity in rates of pathological accumulation as well as test-retest reliability of the biomarker. The relative contributions of these variabilities have not been systematically assessed. This would be particularly relevant if extrapolations from DPM were to be used to make individual-level predictions for research, clinical trials, or potentially future clinical practice. Methods: We conducted simulation studies incorporating empirically-derived noise properties from amyloid biomarkers to assess the contributions of inter- and intra-individual variability. Findings generalized in an autosomal dominant AD cohort with amyloid positron emission tomography (PET), cerebrospinal fluid (CSF), and plasma biomarkers and in a sporadic AD cohort with both amyloid PET and plasma biomarkers. We assessed group level DPM performance via mean average error (MAE) and root mean squared error (RMSE). At the individual level, we evaluated distinctness of distributions of biomarker levels associated with specific disease timings. Results: Inter-individual variability was the dominant source of error in temporal estimates. Intra-individual variability reduced estimate stability. Optimal performance occurred in biomarkers with positive average accumulation rates where a subset of individuals had exceptionally high levels of accumulation. In research study data, amyloid PET outperformed CSF and plasma biomarkers. Interpretation: DPM is fundamentally constrained by dynamic range, variability, and test-retest reliability of the biomarker of interest. Current DPM approaches are more robust at the group level, particularly when applied to biomarkers with more than 10-15% variability like fluid biomarkers. Funding: National Institute on Aging, Alzheimer's Association, German Center for Neurodegenerative Diseases, Raul Carrea Institute for Neurological Research, Japan Agency for Medical Research and Development, Korean Ministry of Health & Welfare and Ministry of Science and ICT, Spanish Institute of Health.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Biomarker Variability Limits Individualized Amyloid Time Estimation in Alzheimer Disease
- Date Crossref
- 13/07/2026
- Éditeur
- openRxiv
- Type
- posted-content
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Washington University in St. Louis pays non établi dans la noticeUniversité ou école supérieure
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German Center for Neurodegenerative Diseases pays non établi dans la noticeStructure de recherche
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Hertie Institute for Clinical Brain Research pays non établi dans la noticeInstitution
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University of Tübingen Hertie-Institute for Clinical Brain Research pays non établi dans la noticeUniversité ou école supérieure
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Massachusetts General Hospital Department of Neurology pays non établi dans la noticeÉtablissement de santé
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UK Dementia Research Institute Dementia Research Centre pays non établi dans la noticeStructure de recherche
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University College London pays non établi dans la noticeUniversité ou école supérieure
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Washington University School of Medicine Department of Neurology pays non établi dans la noticeUniversité ou école supérieure
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Washington University in Saint Louis School of Medicine NeuroGenomics and Informatics Center pays non établi dans la noticeUniversité ou école supérieure
Washington University in St. Louis, German Center for Neurodegenerative Diseases et Hertie Institute for Clinical Brain Research, avec 6 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.