TY - JOUR
T1 - Comparing biological markers of Alzheimer's disease across blood fraction and platforms
T2 - comparing apples to oranges
AU - O'Bryant, Sid E.
AU - Lista, Simone
AU - Rissman, Robert A.
AU - Edwards, Melissa
AU - Zhang, Fan
AU - Hall, James
AU - Zetterberg, Henrik
AU - Lovestone, Simon
AU - Gupta, Veer
AU - Graff-Radford, Neill
AU - Martins, Ralph
AU - Jeromin, Andreas
AU - Waring, Stephen
AU - Oh, Esther
AU - Kling, Mitchel
AU - Baker, Laura D.
AU - Hampel, Harald
AU - The ISTAART Blood Based Biomarker Professional Interest Area
N1 - 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.
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - biomarker discovery
KW - blood
KW - diagnostics
KW - Meso Scale Discovery
KW - multiplex assay platform
KW - plasma
KW - preanalytic processing
KW - proteins
KW - Rules Based Medicine
KW - serum
KW - standardization
UR - http://www.scopus.com/inward/record.url?scp=84959378033&partnerID=8YFLogxK
U2 - 10.1016/j.dadm.2015.12.003
DO - 10.1016/j.dadm.2015.12.003
M3 - Article
C2 - 27019866
AN - SCOPUS:84959378033
SN - 2352-8729
VL - 3
SP - 27
EP - 34
JO - Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring
JF - Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring
ER -