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Title
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FUS pathology defines the majority of tau- and TDP-43-negative frontotemporal lobar degeneration
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Author
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Abstract
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| 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. |
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Language
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English
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Source (journal)
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Acta neuropathologica. - Berlin, 1961, currens
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Publication
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Berlin
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2010
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ISSN
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0001-6322
[print]
1432-0533
[online]
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DOI
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10.1007/S00401-010-0698-6
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Volume/pages
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120
:1
(2010)
, p. 33-41
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ISI
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000278928900004
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Full text (Publisher's DOI)
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Full text (open access)
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