The detection of GRN mutation carriers by progranulin blood protein levels from finger-stick collection

Abstract

INTRODUCTION

Heterozygous mutations in the progranulin gene (GRN) leading to decreased progranulin levels are one of the most frequent causes of inherited frontotemporal dementia (FTD). We evaluated progranulin levels in dried blood spots from capillary finger-stick collection (DBS^capillary).

METHODS

Paired venous Ethylenediaminetetraacetic acid (EDTA) plasma and DBS^capillary samples were collected from each participant with or without pathogenic GRN mutations.

RESULTS

DBS^capillary progranulin levels in GRN mutation carriers (mean [SD] age, 55 [13] years; n = 16) were reduced compared to non-mutation carriers (64 [11] years; n = 44) (2.38 ng/mL [1.0] vs 4.37 [0.68] ng/mL; U = 42; p < 0.0001, ROC AUC = 0.94 [95% CI: 0.83 to 1.00]) and highly associated with venous plasma levels (R = 0.819; p < 0.001).

DISCUSSION

Progranulin levels can be accurately determined from finger-stick blood samples. This can enable regular and remote monitoring of this protein in FTD therapeutic trials and potentially serve as a first-level screening test for GRN mutations.

Highlights

• Progranulin levels measured using capillary dried blood spots were significantly reduced in GRN mutation carriers compared to non-mutation carriers.
• Progranulin levels measured using capillary dried blood spots strongly correlated with levels from venous EDTA plasma.
• DBS^capillary progranulin levels were able to identify GRN mutation carriers with high accuracy.
• DBS^capillary might allow repeated measurements of progranulin levels in a remote and unsupervised setting, circumventing the restrictions of traditional venous blood collection.
• DBS^capillary might be used to assess the biological efficacy of disease-modifying therapies in clinical trials aiming to increase baseline progranulin levels or as a first-level screening for GRN mutations in primary settings.