Blood metabolite markers of preclinical Alzheimer's disease in two longitudinally followed cohorts of older individuals.
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Authors
Casanova, RamonVarma, Sudhir
Simpson, Brittany
Kim, Min
An, Yang
Saldana, Santiago
Riveros, Carlos
Moscato, Pablo
Griswold, Michael
Sonntag, Denise
Wahrheit, Judith
Klavins, Kristaps
Jonsson, Palmi V
Eiriksdottir, Gudny
Aspelund, Thor
Launer, Lenore J
Gudnason, Vilmundur
Legido Quigley, Cristina
Thambisetty, Madhav
Issue Date
2016-07
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Blood metabolite markers of preclinical Alzheimer's disease in two longitudinally followed cohorts of older individuals. 2016, 12 (7):815-22 Alzheimers DementAbstract
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%).Quantitative targeted metabolomics in serum using an identical method as in the index study.
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.
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.
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Efst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinnAdditional Links
http://aanddjournal.net/article/S1552-5260(15)03032-0/pdfRights
Archived with thanks to Alzheimer's & dementia : the journal of the Alzheimer's Associationae974a485f413a2113503eed53cd6c53
10.1016/j.jalz.2015.12.008
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