Neumann Manuela, Tolnay Markus, Mackenzie Ian R A
Institute of Neuropathology, University Hospital of Zürich, Switzerland.
Expert Rev Mol Med. 2009 Jul 29;11:e23. doi: 10.1017/S1462399409001136.
Frontotemporal dementia (FTD) is a clinical syndrome with a heterogeneous molecular basis. Familial FTD has been linked to mutations in several genes, including those encoding the microtubule-associated protein tau (MAPT), progranulin (GRN), valosin-containing protein (VCP) and charged multivescicular body protein 2B (CHMP2B). The associated neuropathology is characterised by selective degeneration of the frontal and temporal lobes (frontotemporal lobar degeneration, FTLD), usually with the presence of abnormal intracellular protein accumulations. The current classification of FTLD neuropathology is based on the identity of the predominant protein abnormality, in the belief that this most closely reflects the underlying pathogenic process. Major subgroups include those characterised by the pathological tau, TDP-43, intermediate filaments and a group with cellular inclusions composed of an unidentified ubiquitinated protein. This review will focus on the current understanding of the molecular basis of each of the major FTLD subtypes. It is anticipated that this knowledge will provide the basis of future advances in the diagnosis and treatment of FTD.
额颞叶痴呆（FTD）是一种具有异质性分子基础的临床综合征。家族性FTD与多个基因的突变有关，包括那些编码微管相关蛋白tau（MAPT）、原颗粒蛋白（GRN）、含缬酪肽蛋白（VCP）和多囊泡体蛋白2B（CHMP2B）的基因。相关的神经病理学特征为额叶和颞叶的选择性退化（额颞叶变性，FTLD），通常伴有异常细胞内蛋白聚集。目前FTLD神经病理学的分类基于主要蛋白异常的特征，认为这最能反映潜在的致病过程。主要亚组包括以病理性tau、TDP-43、中间丝为特征的亚组，以及一组具有由未鉴定的泛素化蛋白组成的细胞内包涵体的亚组。本综述将聚焦于目前对每种主要FTLD亚型分子基础的理解。预计这些知识将为FTD诊断和治疗的未来进展提供基础。
