title: Frontotemporal dementia: implications for understanding Alzheimer disease.
abstract: Frontotemporal dementia (FTD) comprises a group of behavioral, language, and movement disorders. On the basis of the nature of the characteristic protein inclusions, frontotemporal lobar degeneration (FTLD) can be subdivided into the common FTLD-tau and FTLD-TDP as well as the less common FTLD-FUS and FTLD-UPS. Approximately 10% of cases of FTD are inherited in an autosomal-dominant manner. Mutations in seven genes cause FTD, with those in tau (MAPT), chromosome 9 open reading frame 72 (C9ORF72), and progranulin (GRN) being the most common. Mutations in MAPT give rise to FTLD-tau and mutations in C9ORF72 and GRN to FTLD-TDP. The other four genes are transactive response-DNA binding protein-43 (TARDBP), fused in sarcoma (FUS), valosin-containing protein (VCP), and charged multivesicular body protein 2B (CHMP2B). Mutations in TARDBP and VCP give rise to FTLD-TDP, mutations in FUS to FTLD-FUS, and mutations in CHMP2B to FTLD-UPS. The discovery that mutations in MAPT cause neurodegeneration and dementia has important implications for understanding Alzheimer disease.
authors.affiliation: MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom. mg@mrc-lmb.cam.ac
authors.forename: Michel
authors.initials: M
authors.lastname: Goedert
authors.forename: Bernardino
authors.initials: B
authors.lastname: Ghetti
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Spillantini
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics; D000544:Alzheimer Disease / Q000235:genetics* / Q000266:history; D000073885:C9orf72 Protein; D018797:Cell Cycle Proteins / Q000235:genetics; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics; D057180:Frontotemporal Dementia / Q000235:genetics* / Q000266:history; D049672:History, 19th Century; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D016472:Motor Neuron Disease / Q000235:genetics; D009154:Mutation / Q000235:genetics; D010554:Personality Disorders / Q000235:genetics; D000077153:Progranulins; D011506:Proteins / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics; D013494:Supranuclear Palsy, Progressive / Q000235:genetics; D000074405:Valosin Containing Protein; D029867:Xenopus Proteins / Q000235:genetics; D016875:tau Proteins / Q000235:genetics
chemical_list: D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; C507674:CHMP2A protein, human; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D056827:Endosomal Sorting Complexes Required for Transport; C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; C054369:MAPT protein, human; D000077153:Progranulins; D011506:Proteins; D016601:RNA-Binding Proteins; D029867:Xenopus Proteins; C574615:fus protein, Xenopus; D016875:tau Proteins; D000251:Adenosine Triphosphatases; C000614178:VCP protein, human; D000074405:Valosin Containing Protein