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Distinct pathological subtypes of FTLD-FUS.
- Source :
-
Acta neuropathologica [Acta Neuropathol] 2011 Feb; Vol. 121 (2), pp. 207-18. Date of Electronic Publication: 2010 Oct 30. - Publication Year :
- 2011
-
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.
- Subjects :
- Basophils pathology
DNA-Binding Proteins metabolism
Female
Humans
Intranuclear Inclusion Bodies metabolism
Intranuclear Inclusion Bodies pathology
Male
Neurodegenerative Diseases metabolism
Neurodegenerative Diseases pathology
Statistics, Nonparametric
tau Proteins metabolism
Brain metabolism
Brain pathology
Frontotemporal Lobar Degeneration classification
Frontotemporal Lobar Degeneration metabolism
Frontotemporal Lobar Degeneration pathology
RNA-Binding Protein FUS metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1432-0533
- Volume :
- 121
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Acta neuropathologica
- Publication Type :
- Academic Journal
- Accession number :
- 21052700
- Full Text :
- https://doi.org/10.1007/s00401-010-0764-0