title: Comparing biological markers of Alzheimer's disease across blood fraction and platforms: Comparing apples to oranges.
abstract: BACKGROUND
  This study investigated the comparability of potential Alzheimer's disease (AD) biomarkers across blood fractions and assay platforms.
  
  
  METHODS
  Nonfasting serum and plasma samples from 300 participants (150 AD patients and 150 controls) were analyzed. Proteomic markers were obtained via electrochemiluminescence or Luminex technology. Comparisons were conducted via Pearson correlations. The relative importance of proteins within an AD diagnostic profile was examined using random forest importance plots.
  
  
  RESULTS
  On the Meso Scale Discovery multiplex platform, 10 of the 21 markers shared >50% of the variance across blood fractions (serum amyloid A R(2) = 0.99, interleukin (IL)10 R(2) = 0.95, fatty acid-binding protein (FABP) R(2) = 0.94, I309 R(2) = 0.94, IL-5 R(2) = 0.94, IL-6 R(2) = 0.94, eotaxin3 R(2) = 0.91, IL-18 R(2) = 0.87, soluble tumor necrosis factor receptor 1 R(2) = 0.85, and pancreatic polypeptide R(2) = 0.81). When examining protein concentrations across platforms, only five markers shared >50% of the variance (beta 2 microglobulin R(2) = 0.92, IL-18 R(2) = 0.80, factor VII R(2) = 0.78, CRP R(2) = 0.74, and FABP R(2) = 0.70).
  
  
  CONCLUSIONS
  The current findings highlight the importance of considering blood fractions and assay platforms when searching for AD relevant biomarkers.
authors.affiliation: Institute for Healthy Aging, Center for Alzheimer's & Neurodegenerative Disease Research, University of North Texas Health Science Center, TX, USA.
authors.forename: Sid E
authors.initials: SE
authors.lastname: O'Bryant
authors.affiliation: AXA Research Fund & UPMC Chair, Paris, France; Sorbonne Universités, Université Pierre et Marie Curie, Paris 06, Institut de la Mémoire et de la Maladie d'Alzheimer (IM2A) & Institut du Cerveau et de la Moelle épinière (ICM), Département de Neurologie, Hôpital de la Pitié-Salpétrière, Paris, France.
authors.forename: Simone
authors.initials: S
authors.lastname: Lista
authors.affiliation: Alzheimer's Disease Cooperative Study, Department of Neurosciences, UCSD School of Medicine, La Jolla, CA, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Rissman
authors.affiliation: Department of Psychology, University of North Texas, Denton, TX, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Edwards
authors.affiliation: Department of Molecular and Medical Genetics, University of North Texas Health Science Center, Fort Worth, TX, USA.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Institute for Healthy Aging, Center for Alzheimer's & Neurodegenerative Disease Research, University of North Texas Health Science Center, TX, USA; Department of Psychiatry, University of North Texas Health Science Center, Fort Worth, TX, USA.
authors.forename: James
authors.initials: J
authors.lastname: Hall
authors.affiliation: Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; UCL Institute of Neurology, London, UK.
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.affiliation: Department of Psychiatry, University of Oxford, Oxford, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Lovestone
authors.affiliation: Center of Excellence for Alzheimer's Disease Research and Care, School of Medical Sciences, Faculty of Health, Engineering and Sciences, Edith Cowan University, Joondalup, WA, Australia.
authors.forename: Veer
authors.initials: V
authors.lastname: Gupta
authors.affiliation: Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
authors.forename: Neill
authors.initials: N
authors.lastname: Graff-Radford
authors.affiliation: Center of Excellence for Alzheimer's Disease Research and Care, School of Medical Sciences, Faculty of Health, Engineering and Sciences, Edith Cowan University, Joondalup, WA, Australia.
authors.forename: Ralph
authors.initials: R
authors.lastname: Martins
authors.affiliation: Quanterix Corp., Lexington, MA, USA.
authors.forename: Andreas
authors.initials: A
authors.lastname: Jeromin
authors.affiliation: Essentia Institute of Rural Health, Duluth, MN, USA; Texas Alzheimer's Research and Care Consortium, TX, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Waring
authors.affiliation: Division of Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Esther
authors.initials: E
authors.lastname: Oh
authors.affiliation: Behavioral Health Service, Cpl. Michael J. Crescenz VA Medical Center and Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Mitchel
authors.initials: M
authors.lastname: Kling
authors.affiliation: Department of Medicine, Internal Medicine (Geriatrics), Wake Forest School of Medicine, Winston Salem, NC, USA.
authors.forename: Laura D
authors.initials: LD
authors.lastname: Baker
authors.affiliation: AXA Research Fund & UPMC Chair, Paris, France; Sorbonne Universités, Université Pierre et Marie Curie, Paris 06, Institut de la Mémoire et de la Maladie d'Alzheimer (IM2A) & Institut du Cerveau et de la Moelle épinière (ICM), Département de Neurologie, Hôpital de la Pitié-Salpétrière, Paris, France.
authors.forename: Harald
authors.initials: H
authors.lastname: Hampel
keywords: Alzheimer's disease; Biomarker discovery; Blood; Diagnostics; Meso Scale Discovery; Multiplex assay platform; Plasma; Preanalytic processing; Proteins; Rules Based Medicine; Serum; Standardization