FUS pathology defines the majority of tau-and TDP-43-negative frontotemporal lobar degeneration
July 2010
Article
| Related Files |
|---|
View PDF Version
(20100806_030.pdf, 0.2MB) |
|
Redirect to Publisher's version
(Publisher's version.url.txt, 43 bytes) |
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.
- frontotemporal
- bvftd
- inclusion
- frontotemporal lobar degeneration
- disease
- pathology
- dementia
- mutation
- frontotemporal dementia
- degeneration
- aftld-u
- lobar
- neuropathol
- department
- subtype
- ftld-fu
- university
- protein
- mackenzie
- ftld-up
