Comparing biological markers of Alzheimer's disease across blood fraction and platforms: comparing apples to oranges

Sid E. O'Bryant*, Simone Lista, Robert A. Rissman, Melissa Edwards, Fan Zhang, James Hall, Henrik Zetterberg, Simon Lovestone, Veer Gupta, Neill Graff-Radford, Ralph Martins, Andreas Jeromin, Stephen Waring, Esther Oh, Mitchel Kling, Laura D. Baker, Harald Hampel, The ISTAART Blood Based Biomarker Professional Interest Area

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Introduction: 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 R2 = 0.99, interleukin (IL)10 R2 = 0.95, fatty acid-binding protein (FABP) R2 = 0.94, I309 R2 = 0.94, IL-5 R2 = 0.94, IL-6 R2 = 0.94, eotaxin3 R2 = 0.91, IL-18 R2 = 0.87, soluble tumor necrosis factor receptor 1 R2 = 0.85, and pancreatic polypeptide R2 = 0.81). When examining protein concentrations across platforms, only five markers shared >50% of the variance (beta 2 microglobulin R2 = 0.92, IL-18 R2 = 0.80, factor VII R2 = 0.78, CRP R2 = 0.74, and FABP R2 = 0.70). Discussion: The current findings highlight the importance of considering blood fractions and assay platforms when searching for AD relevant biomarkers.

Original languageEnglish
Pages (from-to)27-34
Number of pages8
JournalAlzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring
Publication statusPublished - 2016
Externally publishedYes

Bibliographical note

Copyright the Author(s) 2016. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.


  • Alzheimer's disease
  • biomarker discovery
  • blood
  • diagnostics
  • Meso Scale Discovery
  • multiplex assay platform
  • plasma
  • preanalytic processing
  • proteins
  • Rules Based Medicine
  • serum
  • standardization


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