title: The molecular basis of frontotemporal dementia.
abstract: 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.
authors.affiliation: Institute of Neuropathology, University Hospital of Zürich, Switzerland.
authors.forename: Manuela
authors.initials: M
authors.lastname: Neumann
authors.forename: Markus
authors.initials: M
authors.lastname: Tolnay
authors.forename: Ian R A
authors.initials: IR
authors.lastname: Mackenzie
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics; D003704:Dementia / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D056827:Endosomal Sorting Complexes Required for Transport; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D000077153:Progranulins; D000074405:Valosin Containing Protein; D016875:tau Proteins / Q000235:genetics
chemical_list: C503812:CHMP2B protein, human; D018797:Cell Cycle Proteins; D056827:Endosomal Sorting Complexes Required for Transport; C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; C054369:MAPT protein, human; D009419:Nerve Tissue Proteins; D000077153:Progranulins; D016875:tau Proteins; D000251:Adenosine Triphosphatases; C000614178:VCP protein, human; D000074405:Valosin Containing Protein