Mutations in the granulin gene (GRN) cause familial frontotemporal dementia. Understanding the structural brain changes in presymptomatic GRN carriers would enforce the use of neuroimaging biomarkers for early diagnosis and monitoring. We studied 100 presymptomatic GRN mutation carriers and 94 noncarriers from the Genetic Frontotemporal dementia initiative (GENFI), with MRI structural images. We analyzed 3T MRI structural images using the FreeSurfer pipeline to calculate the whole brain cortical thickness (CTh) for each subject. We also perform a vertex-wise general linear model to assess differences between groups in the relationship between CTh and diverse covariables as gender, age, the estimated years to onset and education. We also explored differences according to TMEM106B genotype, a possible disease modifier. Whole brain CTh did not differ between carriers and noncarriers. Both groups showed age-related cortical thinning. The group-by-age interaction analysis showed that this age-related cortical thinning was significantly greater in GRN carriers in the left superior frontal cortex. TMEM106B did not significantly influence the age-related cortical thinning. Our results validate and expand previous findings suggesting an increased CTh loss associated with age and estimated proximity to symptoms onset in GRN carriers, even before the disease onset.

颗粒蛋白基因 ( GRN )的突变导致家族性额颞叶痴呆。了解症状前GRN携带者的大脑结构变化将强制使用神经影像生物标志物进行早期诊断和监测。我们研究了 100 个症状前GRN来自遗传性额颞叶痴呆倡议 (GENFI) 的突变携带者和 94 名非携带者，以及 MRI 结构图像。我们使用 FreeSurfer 管道分析了 3T MRI 结构图像，以计算每个受试者的全脑皮质厚度 (CTh)。我们还执行了一个顶点通用线性模型，以评估 CTh 与不同协变量（如性别、年龄、估计发病年限和教育）之间关系的组间差异。我们还根据可能的疾病修饰因子 TMEM106B基因型探索了差异。全脑 CTh 在携带者和非携带者之间没有差异。两组都表现出与年龄相关的皮质变薄。逐年龄组交互分析表明，这种与年龄相关的皮质变薄在GRN中显着更大左上额叶皮层的携带者。TMEM106B没有显着影响与年龄相关的皮质变薄。我们的结果验证并扩展了先前的研究结果，表明与年龄相关的 CTh 损失增加以及GRN携带者与症状发作的估计接近程度，甚至在疾病发作之前。