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

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

Acta neuropathologica (2010-05-22)

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, 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

PMID20490813

摘要

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.