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

2019

ALZHEIMER'S & DEMENTIA

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

01 Pubblicazione su rivista

Vergallo A., Megret L., Lista S., Cavedo E., Zetterberg H., Blennow K., Vanmechelen E., De Vos A., Habert M. -O., Potier M. -C., Dubois B., Neri C., Hampel H., Bakardjian H., Benali H., Bertin H., Bonheur J., Boukadida L., Boukerrou N., Cavedo E., Chiesa P., Colliot O., Dubois B., Dubois M., Epelbaum S., Gagliardi G., Genthon R., Habert M. O., Hampel H., Houot M., Kas A., Lamari F., Levy M., Lista S., Metzinger C., Mochel F., Nyasse F., Poisson C., Revillon M., Santos A., Andrade K. S., Sole M., Surtee M., de Schotten M T., Vergallo A., Younsi N., Aguilar L. F., Babiloni C., Baldacci F., Benda N., Black K. L., Bokde A. L. W., Bonuccelli U., Broich K., Cacciola F., Castrillo J., Ceravolo R., Chiesa P. A., Corvol J. -C., Cuello A. C., Cummings J. L., Depypere H., Duggento A., Escott-Price V., Federoff H., Ferretti M. T., Fiandaca M., Frank R. A., Garaci F., Geerts H., Giorgi F. S., Graziani M., Haberkamp M., Herholz K., Karran E., Kim S. H., Koronyo Y., Koronyo-Hamaoui M., Lamari F., Langevin T., Lehericy S., Lorenceau J., Mango D., Mapstone M., Nistico R., O'Bryant S. E., Perry G., Ritchie C., Rossi S., Saidi A., Santarnecchi E., Schneider L. S., Sporns O., Toschi N., Verdooner S. R., Villain N., Welikovitch L. A., Woodcock J., Younesi E.

DOI: 10.1016/j.jalz.2019.03.009

ISSN: 1552-5260

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.

classification and regression trees (CART) machine learning Plasma amyloid β Simoa immunoassay subjective memory complainers