Comparative Analysis of Alzheimer's Disease Cerebrospinal Fluid Biomarkers Measurement by Multiplex SOMAscan Platform and Immunoassay-Based Approach

Jigyasha Timsina, Duber Gomez-Fonseca, Lihua Wang, Anh Do, Dan Western, Ignacio Alvarez, Miquel Aguilar, Pau Pastor, Rachel L. Henson, Elizabeth Herries, Chengjie Xiong, Suzanne E. Schindler, Anne M. Fagan, Randall J. Bateman, Martin Farlow, John C. Morris, Richard Perrin, Krista Moulder, Jason Hassenstab, Jasmeer ChhatwalHiroshi Mori, Yun Ju Sung, Carlos Cruchaga

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Background: The SOMAscan assay has an advantage over immunoassay-based methods because it measures a large number of proteins in a cost-effective manner. However, the performance of this technology compared to the routinely used immunoassay techniques needs to be evaluated. Objective: We performed comparative analyses of SOMAscan and immunoassay-based protein measurements for five cerebrospinal fluid (CSF) proteins associated with Alzheimer's disease (AD) and neurodegeneration: NfL, Neurogranin, sTREM2, VILIP-1, and SNAP-25. Methods: We compared biomarkers measured in ADNI (N=689), Knight-ADRC (N=870), DIAN (N=115), and Barcelona-1 (N=92) cohorts. Raw protein values were transformed using z-score in order to combine measures from the different studies. sTREM2 and VILIP-1 had more than one analyte in SOMAscan; all available analytes were evaluated. Pearson's correlation coefficients between SOMAscan and immunoassays were calculated. Receiver operating characteristic curve and area under the curve were used to compare prediction accuracy of these biomarkers between the two platforms. Results: Neurogranin, VILIP-1, and NfL showed high correlation between SOMAscan and immunoassay measures (r>0.9). sTREM2 had a fair correlation (r>0.6), whereas SNAP-25 showed weak correlation (r=0.06). Measures in both platforms provided similar predicted performance for all biomarkers except SNAP-25 and one of the sTREM2 analytes. sTREM2 showed higher AUC for SOMAscan based measures. Conclusion: Our data indicate that SOMAscan performs as well as immunoassay approaches for NfL, Neurogranin, VILIP-1, and sTREM2. Our study shows promise for using SOMAscan as an alternative to traditional immunoassay-based measures. Follow-up investigation will be required for SNAP-25 and additional established biomarkers.

Original languageEnglish
Pages (from-to)193-207
Number of pages15
JournalJournal of Alzheimer's Disease
Volume89
Issue number1
DOIs
StatePublished - 2022

Keywords

  • Alzheimer's disease
  • SOMAscan
  • assays
  • cerebrospinal fluid biomarkers
  • correlation

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