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

doi:10.1016/j.dadm.2015.12.003

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

Alzheimers Dement (Amst). 2015 Dec 29:3:27-34. doi: 10.1016/j.dadm.2015.12.003. eCollection 2016.

Authors

Sid E O'Bryant¹, Simone Lista², Robert A Rissman³, Melissa Edwards⁴, Fan Zhang⁵, James Hall⁶, Henrik Zetterberg⁷, Simon Lovestone⁸, Veer Gupta⁹, Neill Graff-Radford¹⁰, Ralph Martins⁹, Andreas Jeromin¹¹, Stephen Waring¹², Esther Oh¹³, Mitchel Kling¹⁴, Laura D Baker¹⁵, Harald Hampel²

Affiliations

¹ Institute for Healthy Aging, Center for Alzheimer's & Neurodegenerative Disease Research, University of North Texas Health Science Center, TX, USA.
² 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.
³ Alzheimer's Disease Cooperative Study, Department of Neurosciences, UCSD School of Medicine, La Jolla, CA, USA.
⁴ Department of Psychology, University of North Texas, Denton, TX, USA.
⁵ Department of Molecular and Medical Genetics, University of North Texas Health Science Center, Fort Worth, TX, USA.
⁶ 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.
⁷ Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; UCL Institute of Neurology, London, UK.
⁸ Department of Psychiatry, University of Oxford, Oxford, UK.
⁹ 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.
¹⁰ Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
¹¹ Quanterix Corp., Lexington, MA, USA.
¹² Essentia Institute of Rural Health, Duluth, MN, USA; Texas Alzheimer's Research and Care Consortium, TX, USA.
¹³ Division of Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹⁴ 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.
¹⁵ Department of Medicine, Internal Medicine (Geriatrics), Wake Forest School of Medicine, Winston Salem, NC, USA.

Abstract

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 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).

Discussion: The current findings highlight the importance of considering blood fractions and assay platforms when searching for AD relevant biomarkers.

Keywords: Alzheimer's disease; Biomarker discovery; Blood; Diagnostics; Meso Scale Discovery; Multiplex assay platform; Plasma; Preanalytic processing; Proteins; Rules Based Medicine; Serum; Standardization.

Abstract

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