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.

中文翻译：

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临床实践中额颞叶痴呆的血浆颗粒蛋白前体水平：10 年的法国经验

GRN 突变是家族性额颞叶变性的常见原因。尽管没有明确的共识阈值，但血浆颗粒蛋白前体水平代表了一种有效的生物标志物，可在降低时预测 GRN 突变。我们评估了血浆水平，以确定它是否也可以预测 160 名 GRN 携带者的发病年龄、临床表型或疾病进展。重要的是，颗粒蛋白前体水平受性别影响，在我们的研究中，男性患者的水平低于女性患者。虽然我们发现与发病年龄或临床表型没有相关性，但我们证实，即使在疾病发病前 40 多年的症状前携带者中，水平降低也预示着 GRN 突变。我们还提供了第一个证据，证明在 4 年的时间跨度内，载体在整个纵向轨迹中的水平稳定性。最后，