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Open Access 01-07-2010 | Original Paper

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

Authors: Hazel Urwin, Keith A. Josephs, Jonathan D. Rohrer, Ian R. Mackenzie, Manuela Neumann, Astrid Authier, Harro Seelaar, John C. Van Swieten, Jeremy M. Brown, Peter Johannsen, Jorgen E. Nielsen, Ida E. Holm, Dennis W. Dickson, Rosa Rademakers, Neill R. Graff-Radford, Joseph E. Parisi, Ronald C. Petersen, Kimmo J. Hatanpaa, Charles L. White III, Myron F. Weiner, Felix Geser, Vivianna M. Van Deerlin, John Q. Trojanowski, Bruce L. Miller, William W. Seeley, Julie van der Zee, Samir Kumar-Singh, Sebastiaan Engelborghs, Peter P. De Deyn, Christine Van Broeckhoven, Eileen H. Bigio, Han-Xiang Deng, Glenda M. Halliday, Jillian J. Kril, David G. Munoz, David M. Mann, Stuart M. Pickering-Brown, Valerie Doodeman, Gary Adamson, Shabnam Ghazi-Noori, Elizabeth M. C. Fisher, Janice L. Holton, Tamas Revesz, Martin N. Rossor, John Collinge, Simon Mead, Adrian M. Isaacs, The FReJA Consortium

Published in: Acta Neuropathologica | Issue 1/2010

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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Title: FUS pathology defines the majority of tau- and TDP-43-negative frontotemporal lobar degeneration
Authors: Hazel Urwin
Keith A. Josephs
Jonathan D. Rohrer
Ian R. Mackenzie
Manuela Neumann
Astrid Authier
Harro Seelaar
John C. Van Swieten
Jeremy M. Brown
Peter Johannsen
Jorgen E. Nielsen
Ida E. Holm
Dennis W. Dickson
Rosa Rademakers
Neill R. Graff-Radford
Joseph E. Parisi
Ronald C. Petersen
Kimmo J. Hatanpaa
Charles L. White III
Myron F. Weiner
Felix Geser
Vivianna M. Van Deerlin
John Q. Trojanowski
Bruce L. Miller
William W. Seeley
Julie van der Zee
Samir Kumar-Singh
Sebastiaan Engelborghs
Peter P. De Deyn
Christine Van Broeckhoven
Eileen H. Bigio
Han-Xiang Deng
Glenda M. Halliday
Jillian J. Kril
David G. Munoz
David M. Mann
Stuart M. Pickering-Brown
Valerie Doodeman
Gary Adamson
Shabnam Ghazi-Noori
Elizabeth M. C. Fisher
Janice L. Holton
Tamas Revesz
Martin N. Rossor
John Collinge
Simon Mead
Adrian M. Isaacs
The FReJA Consortium
Publication date: 01-07-2010
Publisher: Springer-Verlag
Published in: Acta Neuropathologica / Issue 1/2010
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-010-0698-6

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

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