Raaphorst Joost, Grupstra Hepke F, Linssen Wim H J P, van Swieten John C, Schmand Ben, de Visser Marianne
Academisch Medisch Centrum/Universiteit van Amsterdam, Afd. Neurologie, Amsterdam, The Netherlands.
Ned Tijdschr Geneeskd. 2010;154:A631.
There is an overlap between amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Some 5-10% of ALS patients show changes in their behaviour and personality that are characteristic of FTD and about 10% of FTD patients develop ALS. Mild cognitive impairment occurs in 30% of ALS patients. The progressive decline of muscle strength in ALS patients and social skills in FTD patients places severe demands on the patient and his or her contacts. In some ALS and FTD patients, ubiquitin-positive inclusions have been found in the hippocampus and anterior horn cells. In patients with familial FTD who have ubiquitin-positive inclusions, mutations have been found in the progranulin (PGRN) gene. TAR-DNA-binding protein-43, encoded by the TARDBP gene, has recently been identified as a constituent of the ubiquitin inclusions. TARDBP and PGRN mutations are found in patients with ALS. The overlapping characteristics provide clues for further research into the pathogenesis of ALS and FTD.
肌萎缩侧索硬化症（ALS）和额颞叶痴呆（FTD）之间存在重叠。约5%-10%的ALS患者会出现具有FTD特征的行为和性格变化，约10%的FTD患者会发展为ALS。30%的ALS患者会出现轻度认知障碍。ALS患者肌肉力量的逐渐下降以及FTD患者社交技能的逐渐下降给患者及其联系人带来了严重负担。在一些ALS和FTD患者中，已在海马体和前角细胞中发现泛素阳性包涵体。在有泛素阳性包涵体的家族性FTD患者中，已在原颗粒蛋白（PGRN）基因中发现突变。由TARDBP基因编码的TAR-DNA结合蛋白43最近被确定为泛素包涵体的一个组成部分。在ALS患者中发现了TARDBP和PGRN突变。这些重叠特征为进一步研究ALS和FTD的发病机制提供了线索。
