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Distinct pathological subtypes of FTLD-FUS
Ian R A Mackenzie1, David G Munoz, Hirofumi Kusaka
1Department of Pathology, Vancouver General Hospital, University of British Columbia, BC, Canada. ian.mackenzie@vch.ca
Acta Neuropathologica
|November 6, 2010
Summary
Fused in sarcoma (FUS) protein pathology is found in rare frontotemporal lobar degeneration (FTLD) subtypes. This study distinguishes atypical FTLD-U, NIFID, and BIBD as related but distinct FTLD-FUS entities based on FUS-immunoreactivity patterns.
Area of Science:
- Neuroscience
- Neuropathology
- Molecular Biology
Background:
- Most frontotemporal lobar degeneration (FTLD) cases involve tau or TDP-43 protein aggregates.
- Approximately 10% of FTLD cases have uncertain molecular origins.
- Fused in sarcoma (FUS) protein pathology has been identified in some tau/TDP-43-negative FTLD subtypes.
Purpose of the Study:
- To compare FUS-immunoreactive (ir) pathology patterns in atypical FTLD-U, NIFID, and BIBD.
- To determine if these FTLD subtypes are discrete entities or part of a pathological continuum.
- To elucidate the relationship between aFTLD-U, NIFID, and BIBD.
Main Methods:
- Comparative analysis of FUS-ir pathology distribution and morphology.
- Examination of FUS-ir inclusions in cerebral neocortex, hippocampus, and subcortical regions.
- Histopathological assessment of neuronal intranuclear inclusions (NII) in FTLD-FUS subtypes.
Main Results:
- All studied FTLD subtypes exhibited FUS-ir pathology in the cerebral neocortex, hippocampus, and subcortical regions.
- Distinct differences in pathology distribution and inclusion morphology were observed among aFTLD-U, NIFID, and BIBD.
- aFTLD-U cases showed less subcortical pathology and typically round inclusions, while NIFID and BIBD had varied morphologies and more frequent NII.
Conclusions:
- Atypical FTLD-U, NIFID, and BIBD are closely related but distinct entities within FTLD-FUS subtypes.
- These entities share a common molecular pathogenesis despite specific pathological differences.
- Retaining the distinct terminology for aFTLD-U, NIFID, and BIBD is recommended for classifying FTLD-FUS subtypes.
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