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Head-to-head comparison of aptamer- and antibody-based proteomic platforms in human cerebrospinal fluid samples from a real-world memory clinic cohort

Puerta, R.; Cano, A.; Garcia-Gonzalez, P.; Garcia-Gutierrez, F.; Capdevila, M.; de Rojas, I.; Olive, C.; Blazquez-Folch, J.; Sotolongo-Grau, O.; Miguel, A.; Montrreal, L.; Martino, P.; Emon, A.; Orellana, A.; Sung, Y. J.; Frikke-Schmidt, R.; Marchant, N.; Lambert, J. C.; Rosende-Roca, M.; Alegret, M.; Fernandez, M. V.; Marquie, M.; Valero, S.; Tarrega, L.; Cruchaga, C.; Ramirez, A.; Boada, M.; Smets, B.; Cabrera-Socorro, A.; Ruiz, A.

2024-07-18 neurology
10.1101/2024.07.18.24310563 medRxiv
Show abstract

High-throughput proteomic platforms have a crucial role in identifying novel Alzheimers disease (AD) biomarkers and pathways. In this study, we evaluated the reproducibility and reliability of aptamer-based (SomaScan(R) 7k) and antibody-based (Olink(R) Explore 3k) proteomic platforms in cerebrospinal fluid (CSF) samples from the Ace Alzheimer Center Barcelona real-world cohort. Intra- and interplatform reproducibility was evaluated through correlations between two independent SomaScan(R) assays analyzing the same samples and between SomaScan(R) and Olink(R) results. Our 12-category metric of reproducibility combining both correlation analyses identified 2,428 highly reproducible SomaScan CSF measures, with over 600 proteins well reproduced on another proteomic platform. The association analyses among AD clinical phenotypes revealed that the significant associations mainly involved reproducible proteins. The validation of reproducibility in these novel proteomics platforms, measured using this scarce biomaterial, is essential for accurate analysis and proper interpretation of innovative results. This classification metric could enhance confidence in multiplexed proteomic platforms and improve the design of future panels.

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