The spectrum and severity of FUS-immunoreactive inclusions in the frontal and temporal lobes of ten cases of neuronal intermediate filament inclusion disease

Richard A. Armstrong, Marla Gearing, Eileen H. Bigio, Felix F. Cruz-Sanchez, Charles Duyckaerts, Ian R.A. Mackenzie, Robert H. Perry, Kari Skullerud, Hedeaki Yokoo, Nigel J. Cairns

Research output: Contribution to journalArticle

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 proteins. Recently, the 'fused in sarcoma' (FUS) protein (encoded by the FUS gene) has been shown to be a component of the inclusions of familial amyotrophic lateral sclerosis with FUS mutation, NIFID, basophilic inclusion body disease, and atypical FTLD with ubiquitin-immunoreactive inclusions (aFTLD-U). To further characterize FUS proteinopathy in NIFID, and to determine whether the pathology revealed by FUS immunohistochemistry (IHC) is more extensive than a-internexin, we have undertaken a quantitative assessment of ten clinically and neuropathologically well-characterized cases using FUS IHC. The densities of NCI were greatest in the dentate gyrus (DG) and in sectors CA1/2 of the hippocampus. Anti-FUS antibodies also labeled glial inclusions (GI), neuronal intranuclear inclusions (NII), and dystrophic neurites (DN). Vacuolation was extensive across upper and lower cortical layers. Significantly greater densities of abnormally enlarged neurons and glial cell nuclei were present in the lower compared with the upper cortical laminae. FUS IHC revealed significantly greater numbers of NCI in all brain regions especially the DG. Our data suggest: (1) significant densities of FUS-immunoreactive NCI in NIFID especially in the DG and CA1/2; (2) infrequent FUS-immunoreactive GI, NII, and DN; (3) widely distributed vacuolation across the cortex, and (4) significantly more NCI revealed by FUS than a-internexin IHC.
Original languageEnglish
Pages (from-to)219-228
Number of pages10
JournalActa Neuropathologica
Volume121
Issue number2
DOIs
Publication statusPublished - Feb 2011

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Intermediate Filaments
Cytomegalovirus Infections
Frontal Lobe
Temporal Lobe
Sarcoma
Inclusion Bodies
Dentate Gyrus
Immunohistochemistry
Neuroglia
Frontotemporal Lobar Degeneration
Intranuclear Inclusion Bodies
Neurites
Ubiquitin
Progressive Myoclonic Epilepsy
Intermediate Filament Proteins
Gliosis
Cell Nucleus
Atrophy
Epitopes
Hippocampus

Bibliographical note

The original publication is available at www.springerlink.com

Keywords

  • neurofilament intermediate filament inclusion disease
  • NIFID
  • fused in sarcoma
  • FUS
  • neuronal cytoplasmic inclusions
  • NCI
  • density
  • neuronal intranuclear inclusions
  • NII

Cite this

Armstrong, R. A., Gearing, M., Bigio, E. H., Cruz-Sanchez, F. F., Duyckaerts, C., Mackenzie, I. R. A., ... Cairns, N. J. (2011). The spectrum and severity of FUS-immunoreactive inclusions in the frontal and temporal lobes of ten cases of neuronal intermediate filament inclusion disease. Acta Neuropathologica, 121(2), 219-228. https://doi.org/10.1007/s00401-010-0753-3
Armstrong, Richard A. ; Gearing, Marla ; Bigio, Eileen H. ; Cruz-Sanchez, Felix F. ; Duyckaerts, Charles ; Mackenzie, Ian R.A. ; Perry, Robert H. ; Skullerud, Kari ; Yokoo, Hedeaki ; Cairns, Nigel J. / The spectrum and severity of FUS-immunoreactive inclusions in the frontal and temporal lobes of ten cases of neuronal intermediate filament inclusion disease. In: Acta Neuropathologica. 2011 ; Vol. 121, No. 2. pp. 219-228.
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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 proteins. Recently, the 'fused in sarcoma' (FUS) protein (encoded by the FUS gene) has been shown to be a component of the inclusions of familial amyotrophic lateral sclerosis with FUS mutation, NIFID, basophilic inclusion body disease, and atypical FTLD with ubiquitin-immunoreactive inclusions (aFTLD-U). To further characterize FUS proteinopathy in NIFID, and to determine whether the pathology revealed by FUS immunohistochemistry (IHC) is more extensive than a-internexin, we have undertaken a quantitative assessment of ten clinically and neuropathologically well-characterized cases using FUS IHC. The densities of NCI were greatest in the dentate gyrus (DG) and in sectors CA1/2 of the hippocampus. Anti-FUS antibodies also labeled glial inclusions (GI), neuronal intranuclear inclusions (NII), and dystrophic neurites (DN). Vacuolation was extensive across upper and lower cortical layers. Significantly greater densities of abnormally enlarged neurons and glial cell nuclei were present in the lower compared with the upper cortical laminae. FUS IHC revealed significantly greater numbers of NCI in all brain regions especially the DG. Our data suggest: (1) significant densities of FUS-immunoreactive NCI in NIFID especially in the DG and CA1/2; (2) infrequent FUS-immunoreactive GI, NII, and DN; (3) widely distributed vacuolation across the cortex, and (4) significantly more NCI revealed by FUS than a-internexin IHC.",
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Armstrong, RA, Gearing, M, Bigio, EH, Cruz-Sanchez, FF, Duyckaerts, C, Mackenzie, IRA, Perry, RH, Skullerud, K, Yokoo, H & Cairns, NJ 2011, 'The spectrum and severity of FUS-immunoreactive inclusions in the frontal and temporal lobes of ten cases of neuronal intermediate filament inclusion disease', Acta Neuropathologica, vol. 121, no. 2, pp. 219-228. https://doi.org/10.1007/s00401-010-0753-3

The spectrum and severity of FUS-immunoreactive inclusions in the frontal and temporal lobes of ten cases of neuronal intermediate filament inclusion disease. / Armstrong, Richard A.; Gearing, Marla; Bigio, Eileen H.; Cruz-Sanchez, Felix F.; Duyckaerts, Charles; Mackenzie, Ian R.A.; Perry, Robert H.; Skullerud, Kari; Yokoo, Hedeaki; Cairns, Nigel J.

In: Acta Neuropathologica, Vol. 121, No. 2, 02.2011, p. 219-228.

Research output: Contribution to journalArticle

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T1 - The spectrum and severity of FUS-immunoreactive inclusions in the frontal and temporal lobes of ten cases of neuronal intermediate filament inclusion disease

AU - Armstrong, Richard A.

AU - Gearing, Marla

AU - Bigio, Eileen H.

AU - Cruz-Sanchez, Felix F.

AU - Duyckaerts, Charles

AU - Mackenzie, Ian R.A.

AU - Perry, Robert H.

AU - Skullerud, Kari

AU - Yokoo, Hedeaki

AU - Cairns, Nigel J.

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