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Distinct pathological subtypes of FTLD-FUS

Distinct pathological subtypes of FTLD-FUS,10.1007/s00401-010-0764-0,Acta Neuropathologica,Ian R. A. Mackenzie,David G. Munoz,Hirofumi Kusaka,Osamu Yo

Distinct pathological subtypes of FTLD-FUS   (Citations: 9)
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Most cases of frontotemporal lobar degeneration (FTLD) are characterized by abnormal intracellular accumulation of either tau or TDP-43 protein. However, in ~10% of cases, composed of a heterogenous collection of uncommon disorders, the molecular basis remains to be uncertain. We recently discovered that the pathological changes in several tau/TDP-43-negative FTLD subtypes are immunoreactive (ir) for the fused in sarcoma (FUS) protein. In this study, we directly compared the pattern of FUS-ir pathology in cases of atypical FTLD-U (aFTLD-U, N = 10), neuronal intermediate filament inclusion disease (NIFID, N = 5) and basophilic inclusion body disease (BIBD, N = 8), to determine whether these are discrete entities or represent a pathological continuum. All cases had FUS-ir pathology in the cerebral neocortex, hippocampus and a similar wide range of subcortical regions. Although there was significant overlap, each group showed specific differences that distinguished them from the others. Cases of aFTLD-U consistently had less pathology in subcortical regions. In addition, the neuronal inclusions in aFTLD-U usually had a uniform, round shape, whereas NIFID and BIBD were characterized by a variety of inclusion morphologies. In all cases of aFTLD-U and NIFID, vermiform neuronal intranuclear inclusions (NII) were readily identified in the hippocampus and neocortex. In contrast, only two cases of BIBD had very rare NII in a single subcortical region. These findings support aFTLD-U, NIFID and BIBD as representing closely related, but distinct entities that share a common molecular pathogenesis. Although cases with overlapping pathology may exist, we recommend retaining the terms aFTLD-U, NIFID and BIBD for specific FTLD-FUS subtypes.
Journal: Acta Neuropathologica - ACTA NEUROPATHOL , vol. 121, no. 2, pp. 207-218, 2011
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    • ...Approximately 10% of FTLD patients show FUS-immunoreactive pathology and are classified as FTLD-FUS (Neumann et al., 2009; Mackenzie et al., 2010)...

    Yanbo Chenet al. Expression of human FUS protein in Drosophila leads to progressive neu...

    • ...None of the cases had any ‘‘vermiform’’ NII that have previously been reported as a characteristic finding of some subtypes of FTLD-FUS [20, 27, 28]...
    • ...FUS-ir pathology is also a characteristic feature of several clinicopathological subtypes of FTLD (FTLD-FUS), including aFTLD-U, NIFID and BIBD [20]...
    • ...spectrum. None of our ALS cases showed involvement of the broad range of neuroanatomical regions that are affected in all cases of FTLD-FUS [20]...
    • ...Vermiform FUS-ir NII are a consistent feature of both aFTLD-U and NIFID [20] but are not present in ALS-FUS...
    • ...Finally, although FUS-ir GCI have been described in previous reports of ALS-FUS [3, 10, 15, 29, 30, 35, 39] and FTLD-FUS [20, 25, 27, 28], this study represents the most detailed analysis of their anatomical distribution and the first attempt to characterize their cellular identity...

    Ian R. A. Mackenzieet al. Pathological heterogeneity in amyotrophic lateral sclerosis with FUS m...

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