Ontology highlight
ABSTRACT: Introduction
Recently, quantitative metabolomics identified a panel of 10 plasma lipids that were highly predictive of conversion to Alzheimer's disease (AD) in cognitively normal older individuals (n = 28, area under the curve [AUC] = 0.92, sensitivity/specificity of 90%/90%).Methods
Quantitative targeted metabolomics in serum using an identical method as in the index study.Results
We failed to replicate these findings in a substantially larger study from two independent cohorts-the Baltimore Longitudinal Study of Aging ([BLSA], n = 93, AUC = 0.642, sensitivity/specificity of 51.6%/65.7%) and the Age, Gene/Environment Susceptibility-Reykjavik Study ([AGES-RS], n = 100, AUC = 0.395, sensitivity/specificity of 47.0%/36.0%). In analyses applying machine learning methods to all 187 metabolite concentrations assayed, we find a modest signal in the BLSA with distinct metabolites associated with the preclinical and symptomatic stages of AD, whereas the same methods gave poor classification accuracies in the AGES-RS samples.Discussion
We believe that ours is the largest blood biomarker study of preclinical AD to date. These findings underscore the importance of large-scale independent validation of index findings from biomarker studies with relatively small sample sizes.
SUBMITTER: Casanova R
PROVIDER: S-EPMC4947451 | biostudies-literature | 2016 Jul
REPOSITORIES: biostudies-literature
Casanova Ramon R Varma Sudhir S Simpson Brittany B Kim Min M An Yang Y Saldana Santiago S Riveros Carlos C Moscato Pablo P Griswold Michael M Sonntag Denise D Wahrheit Judith J Klavins Kristaps K Jonsson Palmi V PV Eiriksdottir Gudny G Aspelund Thor T Launer Lenore J LJ Gudnason Vilmundur V Legido Quigley Cristina C Thambisetty Madhav M
Alzheimer's & dementia : the journal of the Alzheimer's Association 20160121 7
<h4>Introduction</h4>Recently, quantitative metabolomics identified a panel of 10 plasma lipids that were highly predictive of conversion to Alzheimer's disease (AD) in cognitively normal older individuals (n = 28, area under the curve [AUC] = 0.92, sensitivity/specificity of 90%/90%).<h4>Methods</h4>Quantitative targeted metabolomics in serum using an identical method as in the index study.<h4>Results</h4>We failed to replicate these findings in a substantially larger study from two independent ...[more]