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

Journal article
Authors A. Vergallo
L. Megret
S. Lista
E. Cavedo
Henrik Zetterberg
Kaj Blennow
E. Vanmechelen
A. De Vos
M. O. Habert
M. C. Potier
B. Dubois
C. Neri
H. Hampel
B. Dubois
H. Hampel
H. Bakardjian
H. Benali
O. Colliot
H. Marie-O
F. Lamari
F. Mochel
M. C. Potier
M. T. de Schotten
M. Afshar
L. F. Aguilar
L. Akman-Anderson
J. Arenas
J. Avila
C. Babiloni
F. Baldacci
R. Batrla
N. Benda
K. L. Black
A. L. W. Bokde
U. Bonuccelli
K. Broich
F. Cacciola
F. Caraci
J. Castrillo
E. Cavedo
R. Ceravolo
P. A. Chiesa
J. C. Corvol
A. C. Cuello
J. L. Cummings
H. Depypere
B. Dubois
A. Duggento
E. Emanuele
V. Escott-Price
H. Federoff
M. T. Ferretti
M. Fiandaca
R. A. Frank
F. Garaci
H. Geerts
F. S. Giorgi
E. J. Goetzl
M. Graziani
M. Haberkamp
M. O. Habert
H. Hampel
K. Herholz
F. Hernandez
D. Kapogiannis
E. Karran
S. J. Kiddle
S. H. Kim
Y. Koronyo
M. Koronyo-Hamaoui
T. Langevin
S. Lehericy
A. Lucia
S. Lista
J. Lorenceau
D. Mango
M. Mapstone
C. Neri
R. Nistico
S. E. O'Bryant
G. Palmero
G. Perry
C. Ritchie
S. Rossi
A. Saidi
E. Santarnecchi
L. S. Schneider
O. Sporns
N. Toschi
S. R. Verdooner
A. Vergallo
N. Villain
L. A. Welikovitch
J. Woodcock
E. Younesi
Published in Alzheimers & Dementia
Volume 15
Issue 6
Pages 764-775
ISSN 1552-5260
Publication year 2019
Published at Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Pages 764-775
Language en
Keywords Alzheimer's disease, Plasma amyloid beta, Simoa immunoassay, Machine learning, Subjective, blood-based biomarkers, decline, progression
Subject categories Neurosciences


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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