title: Immune profiling in blood identifies sTNF-R1 performing comparably well as biomarker panels for classification of Alzheimer's disease patients.
abstract: 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.
authors.affiliation: Section for Dementia Research, Hertie-Institute of Clinical Brain Research and Department of Psychiatry and Psychotherapy, University of Tübingen, Germany. christoph.laske@med.uni-tuebingen.de
authors.forename: Christoph
authors.initials: C
authors.lastname: Laske
authors.forename: Michael
authors.initials: M
authors.lastname: Schmohl
authors.forename: Thomas
authors.initials: T
authors.lastname: Leyhe
authors.forename: Elke
authors.initials: E
authors.lastname: Stransky
authors.forename: Walter
authors.initials: W
authors.lastname: Maetzler
authors.forename: Daniela
authors.initials: D
authors.lastname: Berg
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Fallgatter
authors.forename: Thomas
authors.initials: T
authors.lastname: Joos
authors.forename: Janko
authors.initials: J
authors.lastname: Dietzsch
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood / Q000145:classification* / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood*; D012042:Registries
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D047888:Receptors, Tumor Necrosis Factor, Type I