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Article

Plasma with Added Protease Inhibitors Improves Alpha- and Beta-CGRP Measurement Compared to Serum: Towards a Reliable Biomarker for Chronic Migraine

by
Lucía de la Guerra-Sasián
,
Gabriel Gárate
,
Jorge Madera
,
Sara Pérez-Pereda
,
Marta Pascual-Mato
,
Vicente González-Quintanilla
,
Julio Pascual
and
María Muñoz-San Martín
*,†
Instituto de Investigación Marqués de Valdecilla (IDIVAL), Hospital Universitario Marqués de Valdecilla & Universidad de Cantabria, 39011 Santander, Spain
*
Author to whom correspondence should be addressed.
Senior authorship is shared between Julio Pascual and María Muñoz-San Martín.
Int. J. Mol. Sci. 2025, 26(20), 9958; https://doi.org/10.3390/ijms26209958 (registering DOI)
Submission received: 5 September 2025 / Revised: 6 October 2025 / Accepted: 10 October 2025 / Published: 13 October 2025
(This article belongs to the Section Biochemistry)

Abstract

The neuropeptide calcitonin gene-related peptide (CGRP), especially a-CGRP, is central in migraine pathophysiology. Although CGRP is a therapeutic target and potential biomarker, inconsistencies in measurement procedures need to be further studied for reliable results. This study aims to analyze factors influencing plasma CGRP measurement. Chronic migraine (CM) patients were recruited in our Headache Unit. Blood samples were collected before and during treatment with CGRP monoclonal antibodies, processed and stored. Levels of CGRP were measured with isoform-specific enzyme-linked immunosorbent assay (ELISA) tests. Statistical tests were used to assess concentration changes and group differences. The addition of protease inhibitors (PIs) to plasma samples significantly increased a-CGRP level detection, with a smaller effect on β-CGRP. No correlation was found between the a- and β-CGRP levels in plasma. The plasma-PI samples showed higher CGRP concentrations than in serum. The a-CGRP levels decreased during treatment while the β-CGRP levels remained stable. a-CGRP and age correlated negatively, but no sex-related differences were observed either for a- or β-CGRP. PI improved CGRP detection in plasma. The a-CGRP levels, which were influenced by age, decreased with specific treatment, suggesting its potential role as a biomarker. In contrast, β-CGRP remained stable, suggesting independent regulation of both isoforms.
Keywords: CGRP; migraine; protease inhibitors; biomarker; plasma; serum CGRP; migraine; protease inhibitors; biomarker; plasma; serum

Share and Cite

MDPI and ACS Style

de la Guerra-Sasián, L.; Gárate, G.; Madera, J.; Pérez-Pereda, S.; Pascual-Mato, M.; González-Quintanilla, V.; Pascual, J.; Muñoz-San Martín, M. Plasma with Added Protease Inhibitors Improves Alpha- and Beta-CGRP Measurement Compared to Serum: Towards a Reliable Biomarker for Chronic Migraine. Int. J. Mol. Sci. 2025, 26, 9958. https://doi.org/10.3390/ijms26209958

AMA Style

de la Guerra-Sasián L, Gárate G, Madera J, Pérez-Pereda S, Pascual-Mato M, González-Quintanilla V, Pascual J, Muñoz-San Martín M. Plasma with Added Protease Inhibitors Improves Alpha- and Beta-CGRP Measurement Compared to Serum: Towards a Reliable Biomarker for Chronic Migraine. International Journal of Molecular Sciences. 2025; 26(20):9958. https://doi.org/10.3390/ijms26209958

Chicago/Turabian Style

de la Guerra-Sasián, Lucía, Gabriel Gárate, Jorge Madera, Sara Pérez-Pereda, Marta Pascual-Mato, Vicente González-Quintanilla, Julio Pascual, and María Muñoz-San Martín. 2025. "Plasma with Added Protease Inhibitors Improves Alpha- and Beta-CGRP Measurement Compared to Serum: Towards a Reliable Biomarker for Chronic Migraine" International Journal of Molecular Sciences 26, no. 20: 9958. https://doi.org/10.3390/ijms26209958

APA Style

de la Guerra-Sasián, L., Gárate, G., Madera, J., Pérez-Pereda, S., Pascual-Mato, M., González-Quintanilla, V., Pascual, J., & Muñoz-San Martín, M. (2025). Plasma with Added Protease Inhibitors Improves Alpha- and Beta-CGRP Measurement Compared to Serum: Towards a Reliable Biomarker for Chronic Migraine. International Journal of Molecular Sciences, 26(20), 9958. https://doi.org/10.3390/ijms26209958

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