PDF(Pubmed)
Abstract：
Alzheimer\'s Disease (AD) and Frontotemporal Dementia (FTD) are the two major neurodegenerative diseases with distinct clinical and neuropathological profiles. The aim of this report is to conduct a population-based investigation in well-characterized APP, PSEN1, PSEN2, MAPT, GRN, and C9orf72 mutation carriers/pedigrees from the north, the center, and the south of Italy. We retrospectively analyzed the data of 467 Italian individuals. We identified 21 different GRN mutations, 20 PSEN1, 11 MAPT, 9 PSEN2, and 4 APP. Moreover, we observed geographical variability in mutation frequencies by looking at each cohort of participants, and we observed a significant difference in age at onset among the genetic groups. Our study provides evidence that age at onset is influenced by the genetic group. Further work in identifying both genetic and environmental factors that modify the phenotypes in all groups is needed. Our study reveals Italian regional differences among the most relevant AD/FTD causative genes and emphasizes how the collaborative studies in rare diseases can provide new insights to expand knowledge on genetic/epigenetic modulators of age at onset.
摘要：
阿尔茨海默病（AD）和额颞叶痴呆（FTD）是两种主要的神经退行性疾病，具有不同的临床和神经病理学特征。本报告的目的是在特征明确的APP中进行基于人群的调查，PSEN1,PSEN2,MAPT,GRN,和来自北方的C9orf72突变携带者/家谱，中心,意大利南部。我们回顾性分析了467名意大利人的数据。我们鉴定了21种不同的GRN突变,20PSEN1,11MAPT,9PSEN2和4APP。此外，我们通过观察每个参与者队列观察到突变频率的地理变异性，我们观察到遗传群体之间发病年龄的显著差异。我们的研究提供了证据，表明发病年龄受遗传群体的影响。需要进一步的工作来鉴定改变所有群体中的表型的遗传和环境因素。我们的研究揭示了最相关的AD/FTD致病基因之间的意大利地区差异，并强调了罕见疾病的合作研究如何提供新的见解，以扩大对发病年龄的遗传/表观遗传调节剂的认识。
