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

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.