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Cited by 68Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsAdvanced Biosensing Techniques and Applications

Comparative analysis of Alzheimer's disease cerebrospinal fluid biomarkers measurement by multiplex SOMAscan platform and immunoassay‐based approach

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Timsina, Jigyasha, Gomez-Fonseca, Duber, Wang, Lihua, Do, Anh, Western, Dan, Alvarez, Ignacio, Aguilar, Miquel, Pastor, Pau +18 more·2022·Journal of Alzheimer’s Disease
DOI 10.3233/jad-220399PMC PMC9562128
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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.

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  • Biomarker status was available for the CSF samples and has been used before in previous studies stratifying by biomarker.

    “Biomarker status was available for the CSF samples and has been used before in previous studies stratifying by biomarker. 10 , 11 , 13 , 48”

    From A genetic and proteomic comparison of key AD biomarkers across tissues (2024) · cites this paper as [13]

    The Methods (Immunoassays; Statistical analysis, page unavailable) report biomarker measurements for CSF samples, but do not establish that biomarker-positive or -negative status was available for those samples. The Discussion (page unavailable) says the authors used a method for defining such status in several previous studies; it does not say those studies stratified these samples by biomarker status. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

  • SOMAscan-based measurements correlate well with complementary approaches.

    “Nonetheless, we note that SOMAscan-based measurements correlate well with complementary approaches26,97.”

    From Proteogenomic analysis of human cerebrospinal fluid identifies neurologically relevant regulation and implicates causal proteins for Alzheimer’s disease (2024) · cites this paper as [97]

    The Results section (“Correlation between SOMAscan and immunoassay measurements”) reports strong correlations for three CSF biomarkers and a weaker but significant correlation for sTREM2. SNAP-25 showed no significant correlation, so the unqualified claim that SOMAscan-based measurements correlate well with complementary approaches overstates these findings. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • This inconsistency with previous studies might be due to known protein measurement issues with the SOMAscan7K assay when compared to immunoassays.

    “This inconsistency with previous studies might be due to known protein measurement issues with the SOMAscan7K assay when compared to immunoassays. 13”

    From A genetic and proteomic comparison of key AD biomarkers across tissues (2024) · cites this paper as [13]

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Authors
Timsina, J., Gomez-Fonseca, D., Wang, L., Do, A., Western, D., Alvarez, I., Aguilar, M., Pastor, P., Henson, R. L., Herries, E., Xiong, C., Schindler, S. E., Fagan, A. M., Bateman, R. J., Farlow, M., Morris, J. C., Perrin, R. J., Moulder, K., Hassenstab, J., Vöglein, J., Chhatwal, J., Mori, H., Initiative, A. D. N., Dominantly Inherited Alzheimer Network Consortia, Sung, Y. J., & Cruchaga, C.
Affiliations
  • Washington University in St. Louis (US)
  • Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA
  • Memory Disorders Unit, Department of Neurology, University Hospital Mutua Terrassa, Terrassa, Spain
  • University Hospital Mútua de Terrassa (ES)
  • Indiana University Health (US)
  • German Center for Neurodegenerative Diseases (DE)
  • Brigham and Women's Hospital (US)
  • Osaka City University (JP)
Corresponding author
Cruchaga, Carlos
ORCID
Venue
Journal of Alzheimer’s Disease
Publisher
SAGE Publications
Published
2022-07-16
Volume
89
Issue
1
Pages
193-207
ISSN
  • 1387-2877 (ISSN-L)
  • 1875-8908
DOI
10.3233/jad-220399
PMC
PMC9562128
OpenAlex
W4285803892
Cited by
68
References
7
Citations by year
2026: 12 · 2025: 25 · 2024: 20 · 2023: 9 · 2022: 1 · 2021: 1
FWCI
8.92
Type
journal article
Language
en
Open access
Licence
journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)
Locations
  • Journal of Alzheimer s Disease (publishedVersion)
  • PubMed (publishedVersion)
  • DZNE Pub (publishedVersion)
  • PubMed Central (acceptedVersion)
  • IUScholarWorks (Indiana University) (submittedVersion)
Funders
  • U.S. Department of Defense (U01 AG024904, W81XWH, W81XWH-12-2-, W81XWH1220012, AG024904)
  • Alzheimer's Association (SG-20-690363-DIAN, U01 AG024904, W81XWH-12-2-0012)
  • Bristol-Myers Squibb (U01 AG024904, AG024904, W81XWH-12-2-0012)
  • Eli Lilly and Company (U01 AG024904, AG024904, W81XWH-12-2-0012)
  • Pfizer (AG024904, W81XWH-12-2-0012, U01 AG024904)
  • Biogen (W81XWH-12-2-0012, U01 AG024904, AG024904)
  • University of Southern California (W81XWH-12-2-0012, U01 AG024904)
  • Meso Scale Diagnostics (U01 AG024904, AG024904, W81XWH-12-2-0012)
  • Alzheimer's Disease Neuroimaging Initiative (P01AG026276, W81XWH-12-2–0012, U01AG024904, AG024904, W81XWH-12-2-, P01AG03991)
  • BioClinica (U01 AG024904, W81XWH-12-2-0012, AG024904)
  • Novartis Pharmaceuticals Corporation (W81XWH-12-2-0012, U01 AG024904, AG024904)
  • Fondation Brain Canada
  • Japan Agency for Medical Research and Development
  • Northern California Institute for Research and Education (U01 AG024904, W81XWH-12-2-0012)
  • Hope Center for Neurological Disorders
  • Korea Health Industry Development Institute
  • Eisai (W81XWH-12-2-0012, U01 AG024904, AG024904)
  • Deutsches Zentrum für Neurodegenerative Erkrankungen
  • Servier (AG024904, W81XWH-12-2-0012, U01 AG024904)
  • H. Lundbeck A/S (U01 AG024904, AG024904, W81XWH-12-2-0012)
  • IXICO (AG024904, W81XWH-12-2-0012, U01 AG024904)
  • Fleni
  • National Institutes of Health (3u01ag024904-10s2, W81XWH, W81XWH-12-2-0012, U01-AG024904, AG024904)
  • Genentech (W81XWH-12-2-0012, AG024904, U01 AG024904)
  • Canadian Institutes of Health Research (U01 AG024904, W81XWH-12-2-0012)
  • Instituto de Salud Carlos III
  • National Institute on Aging (U01-AG-024904, W81XWH-12-2–0012, AG 024904, RF1AG053303, R01AG044546, P01AG003991, U19AG032438, RF1AG074007, U01AG058922, RF1AG058501, R01AG057777, P30AG066444, P01AG026276)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Advanced Biosensing Techniques and Applications
Keywords
Alzheimer's disease, cerebrospinal fluid biomarkers
MeSH terms
Alzheimer Disease, Humans, Immunoassay, ROC Curve, Biomarkers, Amyloid beta-Peptides, tau Proteins, Neurogranin

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