INTRODUCTION: We report in vivo patterns of neuroinflammation and abnormal protein aggregation in seven cases of familial frontotemporal dementia with mutations in MAPT, GRN and C9orf72 genes. METHODS: Using positron emission tomography (PET), we explored the association of the distribution of activated microglia, as measured by the radioligand [11C]PK11195, and the regional distribution of tau- or TDP-43 pathology, indexed using the radioligand [18F]AV-1451. The familial FTD PET data were compared to healthy controls. RESULTS: Familial FTD patients across all mutation groups showed increased [11C]PK11195 binding predominantly in frontotemporal regions, with additional regions showing abnormalities in individuals. Patients with MAPT mutations had a consistent distribution of [18F]AV-1451 binding across the brain, with heterogeneous distributions among carriers of GRN and C9orf72 mutations. DISCUSSION: This case series suggests a consistent role for neuroinflammation in the pathophysiology of familial FTD, warranting further consideration of immunomodulatory therapies for disease modification and prevention.

中文翻译：

---

家族额颞叶痴呆的神经炎症的体内PET成像

简介：我们报告了7例家族性额颞叶痴呆伴有MAPT，GRN和C9orf72基因突变的神经炎症和蛋白质聚集异常的体内模式。方法：使用正电子发射断层扫描（PET），我们探讨了通过放射性配体[11C] PK11195测量的活化小胶质细胞分布与使用放射性配体[18F]索引的tau-或TDP-43病理区域分布的关联。 ] AV-1451。将家族FTD PET数据与健康对照进行比较。结果：所有突变组的家族性FTD患者显示[11C] PK11195结合增加，主要在额颞区，其他区域表现出异常。具有MAPT突变的患者的[18F] AV-1451结合在大脑中分布一致，在GRN和C9orf72突变的携带者之间分布不均。讨论：该病例系列表明神经炎症在家族性FTD的病理生理中具有一致的作用，因此有必要进一步考虑采用免疫调节疗法来改善和预防疾病。