Plasma amyloid beta 40/42 ratio predicts cerebral amyloidosis in cognitively normal individuals at risk for Alzheimer's disease

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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.

Av författaren/redakt...: Vergallo, A.; Megret, L.; Lista, S.; Cavedo, E.; Zetterberg, Henr ...; Blennow, Kaj, 19 ...; visa fler...; Vanmechelen, E.; De Vos, A.; Habert, M. O.; Potier, M. C.; Dubois, B.; Neri, C.; Hampel, H.; Bakardjian, H.; Benali, H.; Colliot, O.; Marie-O, H.; Lamari, F.; Mochel, F.; de Schotten, M. ...; Afshar, M.; Aguilar, L. F.; Akman-Anderson, ...; Arenas, J.; Avila, J.; Babiloni, C.; Baldacci, F.; Batrla, R.; Benda, N.; Black, K. L.; Bokde, A. L. W.; Bonuccelli, U.; Broich, K.; Cacciola, F.; Caraci, F.; Castrillo, J.; Ceravolo, R.; Chiesa, P. A.; Corvol, J. C.; Cuello, A. C.; Cummings, J. L.; Depypere, H.; Duggento, A.; Emanuele, E.; Escott-Price, V.; Federoff, H.; Ferretti, M. T.; Fiandaca, M.; Frank, R. A.; Garaci, F.; Geerts, H.; Giorgi, F. S.; Goetzl, E. J.; Graziani, M.; Haberkamp, M.; Herholz, K.; Hernandez, F.; Kapogiannis, D.; Karran, E.; Kiddle, S. J.; Kim, S. H.; Koronyo, Y.; Koronyo-Hamaoui, ...; Langevin, T.; Lehericy, S.; Lucia, A.; Lorenceau, J.; Mango, D.; Mapstone, M.; Nistico, R.; O'Bryant, S. E.; Palmero, G.; Perry, G.; Ritchie, C.; Rossi, S.; Saidi, A.; Santarnecchi, E.; Schneider, L. S.; Sporns, O.; Toschi, N.; Verdooner, S. R.; Villain, N.; Welikovitch, L. ...; Woodcock, J.; Younesi, E.; visa färre...

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Medicinska och f ...; och Neurovetenskaper

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