Alzheimer's disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi I Sunyer, Barcelona, Spain.
Departament de Biomedicina, Institute of Neuroscience, University of Barcelona, Institute of Biomedical Research August Pi i Sunyer (IDIBAPS), Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Spain.
Neuroimage Clin. 2021;29:102540. doi: 10.1016/j.nicl.2020.102540. Epub 2020 Dec 29.
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.
GRN 基因突变导致家族性额颞叶痴呆。了解无症状 GRN 携带者的结构性脑变化将加强神经影像学生物标志物在早期诊断和监测中的应用。我们研究了来自遗传额颞叶痴呆倡议（GENFI）的 100 名无症状 GRN 突变携带者和 94 名非携带者，他们都接受了 MRI 结构成像检查。我们使用 FreeSurfer 管道分析了 3T MRI 结构图像，以计算每位受试者的全脑皮质厚度（CTh）。我们还进行了顶点的一般线性模型分析，以评估组间 CTh 与性别、年龄、预计发病年限和教育等多种协变量之间的关系差异。我们还根据 TMEM106B 基因型（一种可能的疾病修饰因子）探索了差异。携带者和非携带者之间的全脑 CTh 没有差异。两组均显示出与年龄相关的皮质变薄。组-年龄交互分析显示，在左侧额上回，GRN 携带者的这种与年龄相关的皮质变薄更为显著。TMEM106B 对与年龄相关的皮质变薄没有显著影响。我们的研究结果验证并扩展了先前的发现，表明 GRN 携带者的 CTh 随着年龄的增长和与症状出现的预计时间的临近而增加，甚至在疾病出现之前也是如此。
