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.
Original language | English (US) |
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Pages (from-to) | 33-41 |
Number of pages | 9 |
Journal | Acta Neuropathologica |
Volume | 120 |
Issue number | 1 |
DOIs | |
State | Published - Jul 2010 |
Funding
Anders Gade, Tove Thusgaard, Memory Disorders Research Group, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark. Susanne Gydesen, Psychiatric Centre Ballerup, Copenhagen University Hospital, Ballerup, Denmark. Elisabet Englund, Department of Pathology, Lund University Hospital, Lund, Sweden. This work was undertaken at UCLH/UCL, and was supported by the Department of Health’s NIHR Biomedical Research Centres; the Medical Research Council, UK; the National Institute on Aging, National Institutes of Health [grant numbers P30 AG012300 to UTSW, P30 AG13854 to NWU, P50 AG16574 to Mayo Clinic, AG10124 and AG17546 to U. Penn.]; the National Center for Research Resources, National Institutes of Health [grant number UL1RR024982]; the National Institutes of Health [grant number NIH NS65782-01 J]; the Fund for Scientific Research Flanders (FWO-V); the IAP P6/43 network of the Belgian Science Policy Office (BELSPO); the Winspear Family Center for Research on the Neuropathology of Alzheimer Disease and the McCune Foundation.
Keywords
- FTD
- FTLD
- FTLD-UPS
- FUS
- Frontotemporal
ASJC Scopus subject areas
- Pathology and Forensic Medicine
- Clinical Neurology
- Cellular and Molecular Neuroscience