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Spatial patterns of FUS-immunoreactive neuronal cytoplasmic inclusions (NCI) in neuronal intermediate filament inclusion disease (NIFID)

  • Dementias - Original Article
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Abstract

Neuronal intermediate filament inclusion disease (NIFID), a rare form of frontotemporal lobar degeneration (FTLD), is characterized neuropathologically by focal atrophy of the frontal and temporal lobes, neuronal loss, gliosis, and neuronal cytoplasmic inclusions (NCI) containing epitopes of ubiquitin and neuronal intermediate filament (IF) proteins. Recently, the ‘fused in sarcoma’ (FUS) protein (encoded by the FUS gene) has been shown to be a component of the inclusions of NIFID. To further characterize FUS proteinopathy in NIFID, we studied the spatial patterns of the FUS-immunoreactive NCI in frontal and temporal cortex of 10 cases. In the cerebral cortex, sectors CA1/2 of the hippocampus, and the dentate gyrus (DG), the FUS-immunoreactive NCI were frequently clustered and the clusters were regularly distributed parallel to the tissue boundary. In a proportion of cortical gyri, cluster size of the NCI approximated to those of the columns of cells was associated with the cortico-cortical projections. There were no significant differences in the frequency of different types of spatial patterns with disease duration or disease stage. Clusters of NCI in the upper and lower cortex were significantly larger using FUS compared with phosphorylated, neurofilament heavy polypeptide (NEFH) or α-internexin (INA) immunohistochemistry (IHC). We concluded: (1) FUS-immunoreactive NCI exhibit similar spatial patterns to analogous inclusions in the tauopathies and synucleinopathies, (2) clusters of FUS-immunoreactive NCI are larger than those revealed by NEFH or ΙΝΑ, and (3) the spatial patterns of the FUS-immunoreactive NCI suggest the degeneration of the cortico-cortical projections in NIFID.

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Acknowledgments

We thank Deborah Carter and Toral Patel of the Betty Martz Laboratory for Neurodegenerative Research, Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, and Christine Kaminski of the Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, for expert technical assistance and we thank the families of patients whose generosity made this research possible. Support for this work was provided by grants from the National Institute on Aging of the National Institutes of Health (P50-AG05681 and P01-AG03991 (NJC), AG025688 (MG), and AG13854 (EHB), the Hope Center for Neurological Disorders, the Buchanan Fund, the Charles F. & Joanne Knight Alzheimer’s Disease Research Centre, the McDonnell Center for Molecular and Cellular Neurobiology, and the Barnes-Jewish Foundation.

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Authors and Affiliations

  1. Vision Sciences, Aston University, Birmingham, B4 7ET, UK

    Richard A. Armstrong

  2. Department of Pathology and Laboratory Medicine and Centre for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, GA, USA

    Marla Gearing

  3. Department of Pathology, Northwestern University Medical School, Chicago, IL, USA

    Eileen H. Bigio

  4. Institute of Neurological and Gerontological Sciences, International University of Catalonia, Barcelona, Spain

    Felix F. Cruz-Sanchez

  5. Laboratoire de Neuropathologie, Hôpital de la Salpêtrière, AP-HP, 75651, Paris, France

    Charles Duyckaerts

  6. Department of Pathology and Laboratory Medicine, Vancouver General hospital, Vancouver, BC, Canada

    Ian R. A. Mackenzie

  7. Department of Neuropathology, Newcastle General Hospital, Newcastle-upon-Tyne, NE4 6BE, UK

    Robert H. Perry

  8. Department of Pathology, Rikshospitalet, N-0027, Oslo, Norway

    Kari Skullerud

  9. Department of Pathology, Gunma University School of Medicine, Maebashi, Japan

    Hideaki Yokoo

  10. Charles F. and Joanne Knight Alzheimer’s Disease Research Center, Washington University School of Medicine, St Louis, MO, USA

    Nigel J. Cairns

  11. Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA

    Nigel J. Cairns

  12. Department of Neurology, Washington University School of Medicine, St Louis, MO, USA

    Nigel J. Cairns

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  1. Richard A. Armstrong
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  2. Marla Gearing
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  10. Nigel J. Cairns
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Correspondence to Richard A. Armstrong.

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Armstrong, R.A., Gearing, M., Bigio, E.H. et al. Spatial patterns of FUS-immunoreactive neuronal cytoplasmic inclusions (NCI) in neuronal intermediate filament inclusion disease (NIFID). J Neural Transm 118, 1651–1657 (2011). https://doi.org/10.1007/s00702-011-0690-x

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  • DOI: https://doi.org/10.1007/s00702-011-0690-x

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