Frontotemporal dementia: implications for understanding Alzheimer disease

Cold Spring Harb Perspect Med. 2012 Feb;2(2):a006254. doi: 10.1101/cshperspect.a006254.

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.

Publication types

  • Historical Article
  • Review

MeSH terms

  • Adenosine Triphosphatases / genetics
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / history
  • C9orf72 Protein
  • Cell Cycle Proteins / genetics
  • Chromosomes, Human, Pair 17 / genetics
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Endosomal Sorting Complexes Required for Transport / genetics
  • Frontotemporal Dementia / genetics*
  • Frontotemporal Dementia / history
  • History, 19th Century
  • History, 20th Century
  • History, 21st Century
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics
  • Motor Neuron Disease / genetics
  • Mutation / genetics
  • Personality Disorders / genetics
  • Progranulins
  • Proteins / genetics
  • RNA-Binding Proteins / genetics
  • Supranuclear Palsy, Progressive / genetics
  • Valosin Containing Protein
  • Xenopus Proteins / genetics
  • tau Proteins / genetics

Substances

  • C9orf72 Protein
  • C9orf72 protein, human
  • CHMP2A protein, human
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Endosomal Sorting Complexes Required for Transport
  • GRN protein, human
  • Intercellular Signaling Peptides and Proteins
  • MAPT protein, human
  • Progranulins
  • Proteins
  • RNA-Binding Proteins
  • Xenopus Proteins
  • fus protein, Xenopus
  • tau Proteins
  • Adenosine Triphosphatases
  • VCP protein, human
  • Valosin Containing Protein