Progranulin measurement with a new automated method: a step forward in the diagnostic approach to neurodegenerative disorders

Chiara Cosma; Ilaria Talli; Elisa Pangrazzi; Andrea Padoan; Helena Cerutti; Martina Zaninotto; Carlo Gabelli; Mario Plebani

doi:10.1515/cclm-2024-1143

Article

Progranulin measurement with a new automated method: a step forward in the diagnostic approach to neurodegenerative disorders

Chiara Cosma , Ilaria Talli , Elisa Pangrazzi , Andrea Padoan , Helena Cerutti , Martina Zaninotto , Carlo Gabelli and Mario Plebani

Published/Copyright: January 20, 2025

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From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 63 Issue 6

Abstract

Objectives

Mutations in the GRN gene encoded glycoprotein progranulin (PGRN), cause 5–10 % of all cases of frontotemporal lobar degeneration (FTLD). The aim of our study was to verify the analytical and clinical performance of an automated chemiluminescent immunoassay method for PGRN measurement recently developed (Chorus Evo, Diesse Diagnostica, Italy).

Methods

Five plasma pools and residual plasma samples (K₂EDTA) from 25 control subjects (11 males, 62–79 years; 14 females, 54–76 years) and 151 patients (70 males, 53–81 years; 81 females, 44–82 years) with different neurodegenerative disorders (NDs), were assayed. In 61 out of 151 patients, genetic GRN screening was carried.

Results

Within-run imprecision (CV%) ranged from 3.8 % (11.5 pg/L) to 10.8 % (2.5 pg/L), and between-run, from 5.6 % (68.7 pg/L) to 10.7 % (2.8 pg/L). At genetic screening, 3 out of 61 patients were classified as GRN+ carriers, 18 as “other mutations” and 40 as “no-mutations” carriers. The PGRN median level in GRN+ carriers (15.9 pg/L) was significantly lower than that in control subjects (32.8 pg/L; p=0.006), in GRN− (27.50 pg/L; p=0.007), in other mutation carriers (24.80 pg/L; p=0.05) and in NDs patients (22.40 pg/L; p=0.05) ROC analysis, demonstrates the accuracy of progranulin levels in discriminating between “GRN+” and “GRN−” carriers (AUC 0.985) as well as “GRN+” and “other mutations” carriers (AUC 0.870).

Conclusions

The new automated progranulin method, for robust analytical performance, is suitable for use in the clinical setting, supporting clinicians in making a differential diagnosis in patients with neurodegenerative disorder.

Keywords: progranulin; GRN mutation carriers; neurodegenerative diseases; dementia; chemiluminescence method

Corresponding author: Martina Zaninotto, QI.LAB.MED, Spin-off of the University of Padova, Padova, Italy, E-mail: martina.zaninotto@aopd.veneto.it

Acknowledgments

We acknowledge the uncoditioned support of Diesse Diagnostics for the supply of reagents.

Research ethics: The study was conducted in accordance with Declaration of Helsinki (as revised in 2013) and Ethics Guidelines from the Home Institution.
Informed consent: Informed consent was obtained from all individuals included in this study, or their legal guardians or wards.
Author contributions: The authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Use of Large Language Models, AI and Machine Learning Tools: None declared.
Conflict of interest: The authors state no conflict of interest.
Research funding: None declared.
Data availability: Not applicable.

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Received: 2024-10-01

Accepted: 2025-01-06

Published Online: 2025-01-20

Published in Print: 2025-05-26

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Articles in the same Issue

https://doi.org/10.1515/cclm-2024-1143

Keywords for this article

progranulin; GRN mutation carriers; neurodegenerative diseases; dementia; chemiluminescence method