Plasma progranulin levels for frontotemporal dementia in clinical practice: a 10-year French experience

Abstract GRN mutations are frequent causes of familial FTD. Although there is no clear consensual threshold, plasma progranulin levels represent an efficient biomarker for predicting GRN mutations when decreased. We evaluated plasma levels to determine whether it could also predict age at onset (AAO), clinical phenotype or disease progression in 160 GRN carriers. Importantly, progranulin levels were influenced by gender, with lower levels in male than in female patients in our study. Although we found no correlation with AAO or with clinical phenotype, we confirmed that decreased level predicts GRN mutations, even in presymptomatic carriers more than four decades before disease onset. We also provided first evidence for the stability of levels throughout longitudinal trajectory in carriers, over a 4-year time span. Finally, we confirmed that progranulin levels constitute a reliable, cost-effective marker, suitable as a screening tool in patients with familial FTD, and more broadly in patients without family history or with atypical presentations who are less likely to be referred for molecular diagnosis.