| Title | Frequency of ubiquitin and FUS-positive, TDP-43-negative frontotemporal lobar degeneration |
|---|---|
| Published in | Journal of Neurology: official journal of the European Neurological Society, Vol. 257, No. 5, p.747-753. ISSN 0340-5354. |
| Author | Seelaar, H. (Harro); Klijnsma, K.Y. (Kirsten); Koning, de I. (Inge); Lugt, van der A. (Aad); Chiu, W.Z. (Wang Zheng); Azmani, A. (Asma); Rozemuller, A.J.M. (Annemieke); Swieten, van J.C. |
| Date | 2010-05-01 |
| Language | English |
| Type | article |
| Abstract | Frontotemporal lobar degeneration (FTLD) is a clinically, genetically and pathologically heterogeneous disorder. Within FTLD with ubiquitin-positive inclusions (FTLD-U), a new pathological subtype named FTLD-FUS was recently found with fused in sarcoma (FUS) positive, TDP-43-negative inclusions, and striking atrophy of the caudate nucleus. The aim of this study was to determine the frequency of FTLD-FUS in our pathological FTLD series, and to describe the clinical, neuroimaging and neuropathological features of FTLD-FUS, especially caudate atrophy. Demographic and clinical data collected prospectively from 387 patients with frontotemporal dementia (FTD) yielded 74 brain specimens. Immunostaining was carried out using a panel of antibodies, including AT-8, ubiquitin, p62, FUS, and TDP-43. Cortical and caudate atrophy on MRI (n = 136) was rated as normal, mildmoderate or severe. Of the 37 FTLD-U cases, 33 were reclassified as FTLD-TDP and four (0.11, 95%: 0.00-0.21) as FTLD-FUS, with ubiquitin and FUS-positive, p62 and TDP-43-negative neuronal intranuclear inclusions (NII). All four FTLD-FUS cases had a negative family history, behavioural variant FTD (bvFTD), and three had an age at onset ≤40 years. MRI revealed mild-moderate or severe caudate atrophy in all, with a mean duration from onset till MRI of 63 months (range 16-119 months). In our total clinical FTD cohort, we found 11 patients (0.03; 95% CI: 0.01-0.05) with bvFTD, negative family history, and age at onset ≤40 years. Caudate atrophy was present in 10 out of 136 MRIs, and included all four FUS-cases. The newly identified FTLD-FUS has a frequency of 11% in FTLD-U, and an estimated frequency of three percent in our clinical FTD cohort. The existence of this pathological subtype can be predicted with reasonable certainty by age at onset ≤40 years, negative family history, bvFTD and caudate atrophy on MRI. |
| Publication | http://hdl.handle.net/1765/20736 |
| Persistent Identifier | urn:NBN:nl:ui:15-1765/20736 |
| Metadata | XML |
| Repository | Erasmus University Rotterdam |
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