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01.02.2011 | Original Paper

Distinct pathological subtypes of FTLD-FUS

verfasst von: Ian R. A. Mackenzie, David G. Munoz, Hirofumi Kusaka, Osamu Yokota, Kenji Ishihara, Sigrun Roeber, Hans A. Kretzschmar, Nigel J. Cairns, Manuela Neumann

Erschienen in: Acta Neuropathologica | Ausgabe 2/2011

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Abstract

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.

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Titel: Distinct pathological subtypes of FTLD-FUS
verfasst von: Ian R. A. Mackenzie
David G. Munoz
Hirofumi Kusaka
Osamu Yokota
Kenji Ishihara
Sigrun Roeber
Hans A. Kretzschmar
Nigel J. Cairns
Manuela Neumann
Publikationsdatum: 01.02.2011
Verlag: Springer-Verlag
Erschienen in: Acta Neuropathologica / Ausgabe 2/2011
Print ISSN: 0001-6322
Elektronische ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-010-0764-0

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