期刊
ALZHEIMERS & DEMENTIA
卷 15, 期 6, 页码 764-775出版社
WILEY
DOI: 10.1016/j.jalz.2019.03.009
关键词
Alzheimer's disease; Plasma amyloid beta; Simoa immunoassay; Machine learning; Subjective memory complainers; Amyloid PET; Classification and regression trees (CART)
资金
- program PHOENIX
- la Fondation pour la Recherche sur Alzheimer
- Agency for Innovation and Technology [IWT OO 140105]
- Flanders Innovation and Entrepreneurship [VLAIO 160548]
- European Research Council
- Medical Research Council (UK)
- INSERM
- CNRS
- AXA Research Fund
- Fondation partenariale Sorbonne Universite
- Fondation pour la Recherche sur Alzheimer, Paris, France
- Ce travail a beneficie d'une aide de l'Etat Investissements d'avenir [ANR-10-IAIHU-06]
- program Investissements d'avenir (Agence Nationale de la Recherche-10-IA Agence Institut Hospitalo-Universitaire-6) [ANR-10-IAIHU-06]
- Swedish Research Council
- Sorbonne Universite
- Investissement d'Avenir program [ANR-10-AIHU-06]
- Foundation Plan-Alzheimer
- AVID/Lilly
- Pfizer
- Avid
- MSD Avenir
- Functional Neuromodulation
- Axovant
- Eli Lilly and company
- Takeda
- Zinfandel
- GE-Healthcare
- Oryzon Genomics
Introduction: Blood-based biomarkers of pathophysiological brain amyloid beta (A beta) accumulation, particularly for preclinical target and large-scale interventions, are warranted to effectively enrich Alzheimer's disease clinical trials and management. Methods: We investigated whether plasma concentrations of the A beta(1-40)/A beta(1-42) ratio, assessed using the single-molecule array (Simoa) immunoassay, may predict brain A beta positron emission tomography status in a large-scale longitudinal monocentric cohort (N = 276) of older individuals with subjective memory complaints. We performed a hypothesis-driven investigation followed by a no-apriori hypothesis study using machine learning. Results: The receiver operating characteristic curve and machine learning showed a balanced accuracy of 76.5% and 81%, respectively, for the plasma A beta(1-40)/A beta(1-42) ratio. The accuracy is not affected by the apolipoprotein E (APOE) epsilon 4 allele, sex, or age. Discussion: Our results encourage an independent validation cohort study to confirm the indication that the plasma A beta(1-40)/A beta(1-42) ratio, assessed via Simoa, may improve future standard of care and clinical trial design. (C) 2019 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
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