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

• Published in: Neurobiology of aging 2020-07, Vol.91, p.167.e1-167.e9
• Main Authors: Sellami, Leila, Rucheton, Benoît, Ben Younes, Imen, Camuzat, Agnès, Saracino, Dario, Rinaldi, Daisy, Epelbaum, Stephane, Azuar, Carole, Levy, Richard, Auriacombe, Sophie, Hannequin, Didier, Pariente, Jérémie, Barbier, Mathieu, Boutoleau-Bretonnière, Claire, Couratier, Philippe, Pasquier, Florence, Deramecourt, Vincent, Sauvée, Mathilde, Sarazin, Marie, Lagarde, Julien, Roué-Jagot, Carole, Forlani, Sylvie, Jornea, Ludmila, David, Isabelle, LeGuern, Eric, Dubois, Bruno, Brice, Alexis, Clot, Fabienne, Lamari, Foudil, Le Ber, Isabelle
• Format: Article
• Language: English
• Subjects: Adult; Age of Onset; Aged; C9orf72; Female; France; Frontotemporal dementia; Frontotemporal Dementia / diagnosis; Frontotemporal Dementia / genetics; Frontotemporal lobar degeneration; Frontotemporal Lobar Degeneration / diagnosis; Frontotemporal Lobar Degeneration / genetics; Heterozygote; Humans; Life Sciences; Male; Middle Aged; Mutation; Plasma progranulin levels; Predictive Value of Tests; Progranulin (GRN); Progranulins / blood; Progranulins / genetics; Santé publique et épidémiologie; Sex Characteristics; Time Factors
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2020.02.014

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. •Plasma progranulin levels were analyzed in 293 GRN carriers and controls.•Progranulin levels were stable in carriers and controls over a 4-year time span.•Plasma progranulin did not correlate with age at onset and FTD phenotypes.•Different thresholds were suggested for male and female carriers.