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FUS pathology defines the majority of tau- and TDP-43-negative frontotemporal lobar degeneration.

Authors
  • Urwin, Hazel1
  • Josephs, Keith A
  • Rohrer, Jonathan D
  • Mackenzie, Ian R
  • Neumann, Manuela
  • Authier, Astrid
  • Seelaar, Harro
  • Van Swieten, John C
  • Brown, Jeremy M
  • Johannsen, Peter
  • Nielsen, Jorgen E
  • Holm, Ida E
  • Dickson, Dennis W
  • Rademakers, Rosa
  • Graff-Radford, Neill R
  • Parisi, Joseph E
  • Petersen, Ronald C
  • Hatanpaa, Kimmo J
  • White, Charles L 3rd
  • Weiner, Myron F
  • And 27 more
  • 1 UCL Institute of Neurology, London, UK.
Type
Published Article
Journal
Acta Neuropathologica
Publisher
Springer-Verlag
Publication Date
July 2010
Volume
120
Issue
1
Pages
33–41
Identifiers
DOI: 10.1007/s00401-010-0698-6
PMID: 20490813
Source
Medline
License
Unknown

Abstract

Through an international consortium, we have collected 37 tau- and TAR DNA-binding protein 43 (TDP-43)-negative frontotemporal lobar degeneration (FTLD) cases, and present here the first comprehensive analysis of these cases in terms of neuropathology, genetics, demographics and clinical data. 92% (34/37) had fused in sarcoma (FUS) protein pathology, indicating that FTLD-FUS is an important FTLD subtype. This FTLD-FUS collection specifically focussed on aFTLD-U cases, one of three recently defined subtypes of FTLD-FUS. The aFTLD-U subtype of FTLD-FUS is characterised clinically by behavioural variant frontotemporal dementia (bvFTD) and has a particularly young age of onset with a mean of 41 years. Further, this subtype had a high prevalence of psychotic symptoms (36% of cases) and low prevalence of motor symptoms (3% of cases). We did not find FUS mutations in any aFTLD-U case. To date, the only subtype of cases reported to have ubiquitin-positive but tau-, TDP-43- and FUS-negative pathology, termed FTLD-UPS, is the result of charged multivesicular body protein 2B gene (CHMP2B) mutation. We identified three FTLD-UPS cases, which are negative for CHMP2B mutation, suggesting that the full complement of FTLD pathologies is yet to be elucidated.

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