Andrea Vergallo1, Lucile Mégret2, Simone Lista3, Enrica Cavedo3, Henrik Zetterberg4, Kaj Blennow5, Eugeen Vanmechelen6, Ann De Vos6, Marie-Odile Habert7, Marie-Claude Potier8, Bruno Dubois3, Christian Neri2, Harald Hampel9. 1. Sorbonne University, GRC no 21, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital, Boulevard de l'hôpital, Paris, France; Brain & Spine Institute (ICM), INSERM U 1127, CNRS UMR 7225, Boulevard de l'hôpital, Paris, France; Institute of Memory and Alzheimer's Disease (IM2A), Department of Neurology, Pitié-Salpêtrière Hospital, AP-HP, Boulevard de l'hôpital, Paris, France. Electronic address: andrea.vergallo@icm-institute.org. 2. Sorbonnes Université, CNRS UMR 8256, INSERM ERL U1164, Team Compensation in Neurodegenerative diseases and Aging (Brain-C), Paris, France. 3. Sorbonne University, GRC no 21, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital, Boulevard de l'hôpital, Paris, France; Brain & Spine Institute (ICM), INSERM U 1127, CNRS UMR 7225, Boulevard de l'hôpital, Paris, France; Institute of Memory and Alzheimer's Disease (IM2A), Department of Neurology, Pitié-Salpêtrière Hospital, AP-HP, Boulevard de l'hôpital, Paris, France. 4. Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK; UK Dementia Research Institute, London, UK. 5. Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden. 6. ADx NeuroSciences NV, Ghent, Belgium. 7. Sorbonne Université, CNRS, INSERM, Laboratoire d'Imagerie Biomédicale, Paris, France; Centre pour l'Acquisition et le Traitement des Images, Paris, France; AP-HP, Hôpital Pitié-Salpêtrière, Département de Médecine Nucléaire, Paris, France. 8. ICM Institut du Cerveau et de la Moelle épinière, CNRS UMR7225, INSERM U1127, UPMC, Hôpital de la Pitié-Salpêtrière, Paris, France. 9. Sorbonne University, GRC no 21, Alzheimer Precision Medicine (APM), AP-HP, Pitié-Salpêtrière Hospital, Boulevard de l'hôpital, Paris, France.
Abstract
INTRODUCTION: Blood-based biomarkers of pathophysiological brain amyloid β (Aβ) 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 Aβ1-40/Aβ1-42 ratio, assessed using the single-molecule array (Simoa) immunoassay, may predict brain Aβ 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-a-priori 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 Aβ1-40/Aβ1-42 ratio. The accuracy is not affected by the apolipoprotein E (APOE) ε4 allele, sex, or age. DISCUSSION: Our results encourage an independent validation cohort study to confirm the indication that the plasma Aβ1-40/Aβ1-42 ratio, assessed via Simoa, may improve future standard of care and clinical trial design.
INTRODUCTION: Blood-based biomarkers of pathophysiological brain amyloid β (Aβ) 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 Aβ1-40/Aβ1-42 ratio, assessed using the single-molecule array (Simoa) immunoassay, may predict brain Aβ 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-a-priori 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 Aβ1-40/Aβ1-42 ratio. The accuracy is not affected by the apolipoprotein E (APOE) ε4 allele, sex, or age. DISCUSSION: Our results encourage an independent validation cohort study to confirm the indication that the plasma Aβ1-40/Aβ1-42 ratio, assessed via Simoa, may improve future standard of care and clinical trial design.
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