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

2020; Elsevier BV; Volume: 91; Linguagem: Inglês

10.1016/j.neurobiolaging.2020.02.014

1558-1497

Leila Sellami, Benoît Rucheton, Imen Ben Younes, Agnès Camuzat, Dario Saracino, Daisy Rinaldi, Stéphane Epelbaum, Carole Azuar, Richard Lévy, Sophie Auriacombe, Didier Hannequin, Jérémie Pariente, Mathieu Barbier, Claire Boutoleau‐Bretonnière, Philippe Couratier, Florence Pasquier, Vincent Deramecourt, Mathilde Sauvée, Marie Sarazin, Julien Lagarde, Carole Roué-Jagot, Sylvie Forlani, Ludmila Jornéa, I. Rodenhiser David, Eric LeGuern, Bruno Dubois, Alexis Brice, Fabienne Clot, Foudil Lamari, Isabelle Le Ber,

Neurological diseases and metabolism

GRN mutations are frequent causes of familial frontotemporal degeneration. 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, 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 age at onset 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 frontotemporal degeneration, and more broadly in patients without family history or with atypical presentations who are less likely to be referred for molecular diagnosis.