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- Title
FUS pathology defines the majority of tau- and TDP-43-negative frontotemporal lobar degeneration.
- Authors
Urwin, Hazel; 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; Geser, Felix; Van Deerlin, Vivianna M; Trojanowski, John Q; Miller, Bruce L; Seeley, William W; van der Zee, Julie; Kumar-Singh, Samir; Engelborghs, Sebastiaan; De Deyn, Peter P; Van Broeckhoven, Christine; Bigio, Eileen H; Deng, Han-Xiang; Halliday, Glenda M; Kril, Jillian J; Munoz, David G; Mann, David M; Pickering-Brown, Stuart M; Doodeman, Valerie; Adamson, Gary; Ghazi-Noori, Shabnam; Fisher, Elizabeth M C; Holton, Janice L; Revesz, Tamas; Rossor, Martin N; Collinge, John; Mead, Simon; Isaacs, Adrian M; FReJA Consortium
- 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.
- Publication
Acta neuropathologica, 2010, Vol 120, Issue 1, p33
- ISSN
1432-0533
- Publication type
Journal Article
- DOI
10.1007/s00401-010-0698-6