TY - JOUR
T1 - Aptamarker prediction of brain amyloid-β status in cognitively normal individuals at risk for Alzheimer’s disease
AU - the INSIGHT-preAD study group
AU - Alzheimer Precision Medicine Initiative (APMI)
AU - Penner, Gregory
AU - Lecocq, Soizic
AU - Chopin, Anaëlle
AU - Vedoya, Ximena
AU - Lista, Simone
AU - Vergallo, Andrea
AU - Cavedo, Enrica
AU - Lejeune, Francois Xavier
AU - Dubois, Bruno
AU - Hampel, Harald
AU - Bakardjian, Hovagim
AU - Benali, Habib
AU - Bertin, Hugo
AU - Bonheur, Joel
AU - Boukadida, Laurie
AU - Boukerrou, Nadia
AU - Chiesa, Patrizia A.
AU - Colliot, Olivier
AU - Dubois, Marion
AU - Epelbaum, Stéphane
AU - Gagliardi, Geoffroy
AU - Genthon, Remy
AU - Habert, Marie Odile
AU - Houot, Marion
AU - Kas, Aurélie
AU - Lamari, Foudil
AU - Levy, Marcel
AU - Metzinger, Christiane
AU - Mochel, Fanny
AU - Nyasse, Francis
AU - Poisson, Catherine
AU - Potier, Marie Claude
AU - Revillon, Marie
AU - Santos, Antonio
AU - Andrade, Katia Santos
AU - Sole, Marine
AU - Surtee, Mohmed
AU - de Schotten, Michel Thiebaut
AU - Younsi, Nadjia
AU - Afshar, Mohammad
AU - Aguilar, Lisi Flores
AU - Akman-Anderson, Leyla
AU - Aremas, Joaquín
AU - Ávila, Jesús
AU - Babiloni, Claudio
AU - Baldacci, Filippo
AU - Batrla, Richard
AU - Benda, Norbert
AU - Black, Keith L.
AU - O'Bryant, Sid E.
N1 - Publisher Copyright:
Copyright: © 2021 Penner et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2021/1
Y1 - 2021/1
N2 - The traditional approach to biomarker discovery for any pathology has been through hypothesis-based research one candidate at a time. The objective of this study was to develop an agnostic approach for the simultaneous screening of plasma for consistent molecular differences between a group of individuals exhibiting a pathology and a group of healthy individuals. To achieve this, we focused on developing a predictive tool based on plasma for the amount of brain amyloid-β deposition as observed in PET scans. The accumulation of brain amyloid-β (Aβ) plaques is a key risk factor for the development of Alzheimer’s disease. A contrast was established between cognitively normal individuals above the age of 70 that differed for the amount of brain amyloid-β observed in PET scans (INSIGHT study group). Positive selection was performed against a pool of plasma from individuals with high brain amyloid and negative selection against a pool of plasma from individuals with low brain amyloid This enriched, selected library was then applied to plasma samples from 11 individuals with high levels of brain amyloid and 11 individuals with low levels of brain Aβ accumulation. Each of these individually selected libraries was then characterized by next generation sequencing, and the relative frequency of 10,000 aptamer sequences that were observed in each selection was screened for ability to explain variation in brain amyloid using sparse partial least squares discriminant analysis. From this analysis a subset of 44 aptamers was defined, and the individual aptamers were synthesized. This subset was applied to plasma samples from 70 cognitively normal individuals all above the age of 70 that differed for brain amyloid deposition. 54 individuals were used as a training set, and 15 as a test set. Three of the 15 individuals in the test set were mis-classified resulting in an overall accuracy of 80% with 86% sensitivity and 75% specificity. The aptamers included in the subset serve directly as biomarkers, thus we have named them Aptamarkers. There are two potential applications of these results: extending the predictive capacity of these aptamers across a broader range of individuals, and/or using the individual aptamers to identify targets through covariance analysis and reverse omics approaches. We are currently expanding applications of the Aptamarker platform to other diseases and target matrices.
AB - The traditional approach to biomarker discovery for any pathology has been through hypothesis-based research one candidate at a time. The objective of this study was to develop an agnostic approach for the simultaneous screening of plasma for consistent molecular differences between a group of individuals exhibiting a pathology and a group of healthy individuals. To achieve this, we focused on developing a predictive tool based on plasma for the amount of brain amyloid-β deposition as observed in PET scans. The accumulation of brain amyloid-β (Aβ) plaques is a key risk factor for the development of Alzheimer’s disease. A contrast was established between cognitively normal individuals above the age of 70 that differed for the amount of brain amyloid-β observed in PET scans (INSIGHT study group). Positive selection was performed against a pool of plasma from individuals with high brain amyloid and negative selection against a pool of plasma from individuals with low brain amyloid This enriched, selected library was then applied to plasma samples from 11 individuals with high levels of brain amyloid and 11 individuals with low levels of brain Aβ accumulation. Each of these individually selected libraries was then characterized by next generation sequencing, and the relative frequency of 10,000 aptamer sequences that were observed in each selection was screened for ability to explain variation in brain amyloid using sparse partial least squares discriminant analysis. From this analysis a subset of 44 aptamers was defined, and the individual aptamers were synthesized. This subset was applied to plasma samples from 70 cognitively normal individuals all above the age of 70 that differed for brain amyloid deposition. 54 individuals were used as a training set, and 15 as a test set. Three of the 15 individuals in the test set were mis-classified resulting in an overall accuracy of 80% with 86% sensitivity and 75% specificity. The aptamers included in the subset serve directly as biomarkers, thus we have named them Aptamarkers. There are two potential applications of these results: extending the predictive capacity of these aptamers across a broader range of individuals, and/or using the individual aptamers to identify targets through covariance analysis and reverse omics approaches. We are currently expanding applications of the Aptamarker platform to other diseases and target matrices.
UR - http://www.scopus.com/inward/record.url?scp=85099332108&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0243902
DO - 10.1371/journal.pone.0243902
M3 - Article
C2 - 33395442
AN - SCOPUS:85099332108
SN - 1932-6203
VL - 16
JO - PLoS ONE
JF - PLoS ONE
IS - 1 January
M1 - e0243902
ER -