BACKGROUND: Alzheimer's disease (AD) has been linked to a state of cerebral and systemic inflammation. The objective of the present study was to determine whether singular markers or a set of inflammatory biomarkers in peripheral blood allow discrimination between AD patients and healthy controls at the individual level. METHODS: Using bead based multiplexed sandwich immunoassays, 25 inflammatory biomarkers were measured in 164 serum samples from individuals with early AD and age-matched cognitively healthy elderly controls. The data set was randomly split into a training set for feature selection and classification training and a test set for class prediction of blinded samples (1 : 1 ratio) to evaluate the chosen predictors and parameters. Multivariate data analysis was performed with use of a support vector machine (SVM). RESULTS: After selection of sTNF-R1 as most discriminative parameter in the training set, the application of SVM to the independent test dataset resulted in a 90.0% correct classification for individual AD and control subjects. CONCLUSIONS: We identified sTNF-R1 from a marker set consisting of 25 inflammatory biomarkers, which allowed SVM-based discrimination of AD patients from healthy controls on a single-subject classification level comparably well as biomarker panels with a clinically relevant accuracy and validity. Although larger sample populations will be needed to confirm this diagnostic accuracy, our study suggests that sTNF-R1 in serum-either as singular marker or incorporated into a biomarker panel-could be a powerful new biomarker for detection of AD. In addition, selective inhibition of TNF-R1 function may represent a new therapeutic approach in AD.
BACKGROUND:Alzheimer's disease (AD) has been linked to a state of cerebral and systemic inflammation. The objective of the present study was to determine whether singular markers or a set of inflammatory biomarkers in peripheral blood allow discrimination between ADpatients and healthy controls at the individual level. METHODS: Using bead based multiplexed sandwich immunoassays, 25 inflammatory biomarkers were measured in 164 serum samples from individuals with early AD and age-matched cognitively healthy elderly controls. The data set was randomly split into a training set for feature selection and classification training and a test set for class prediction of blinded samples (1 : 1 ratio) to evaluate the chosen predictors and parameters. Multivariate data analysis was performed with use of a support vector machine (SVM). RESULTS: After selection of sTNF-R1 as most discriminative parameter in the training set, the application of SVM to the independent test dataset resulted in a 90.0% correct classification for individual AD and control subjects. CONCLUSIONS: We identified sTNF-R1 from a marker set consisting of 25 inflammatory biomarkers, which allowed SVM-based discrimination of ADpatients from healthy controls on a single-subject classification level comparably well as biomarker panels with a clinically relevant accuracy and validity. Although larger sample populations will be needed to confirm this diagnostic accuracy, our study suggests that sTNF-R1 in serum-either as singular marker or incorporated into a biomarker panel-could be a powerful new biomarker for detection of AD. In addition, selective inhibition of TNF-R1 function may represent a new therapeutic approach in AD.
Authors: Sid E O'Bryant; Guanghua Xiao; Fan Zhang; Melissa Edwards; Dwight C German; Xiangling Yin; Tori Como; Joan Reisch; Ryan M Huebinger; Neill Graff-Radford; Dennis Dickson; Robert Barber; James Hall; Padraig O'Suilleabhain; Paula Grammas Journal: J Alzheimers Dis Date: 2014 Impact factor: 4.472
Authors: John A McIntyre; Curtis J Ramsey; Bruce D Gitter; Andrew J Saykin; Dawn R Wagenknecht; Paul A Hyslop Journal: Autoimmunity Date: 2015-02-12 Impact factor: 2.815
Authors: Heather M Snyder; Maria C Carrillo; Francine Grodstein; Kim Henriksen; Andreas Jeromin; Simon Lovestone; Michelle M Mielke; Sid O'Bryant; Manual Sarasa; Magnus Sjøgren; Holly Soares; Jessica Teeling; Eugenia Trushina; Malcolm Ward; Tim West; Lisa J Bain; Diana W Shineman; Michael Weiner; Howard M Fillit Journal: Alzheimers Dement Date: 2014-01 Impact factor: 21.566
Authors: Sid E O'Bryant; Veer Gupta; Kim Henriksen; Melissa Edwards; Andreas Jeromin; Simone Lista; Chantal Bazenet; Holly Soares; Simon Lovestone; Harald Hampel; Thomas Montine; Kaj Blennow; Tatiana Foroud; Maria Carrillo; Neill Graff-Radford; Christoph Laske; Monique Breteler; Leslie Shaw; John Q Trojanowski; Nicole Schupf; Robert A Rissman; Anne M Fagan; Pankaj Oberoi; Robert Umek; Michael W Weiner; Paula Grammas; Holly Posner; Ralph Martins Journal: Alzheimers Dement Date: 2014-10-01 Impact factor: 21.566
Authors: Catarina M Abreu; Ricardo Soares-Dos-Reis; Pedro N Melo; João B Relvas; Joana Guimarães; Maria José Sá; Andrea P Cruz; Inês Mendes Pinto Journal: Front Mol Neurosci Date: 2018-05-16 Impact factor: 5.639