title: The spectrum and severity of FUS-immunoreactive inclusions in the frontal and temporal lobes of ten cases of neuronal intermediate filament inclusion disease.
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 α-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 α-internexin IHC.
authors.affiliation: Aston University, Birmingham, UK. R.A.Armstrong@aston.ac.uk
authors.forename: Richard A
authors.initials: RA
authors.lastname: Armstrong
authors.forename: Marla
authors.initials: M
authors.lastname: Gearing
authors.forename: Eileen H
authors.initials: EH
authors.lastname: Bigio
authors.forename: Felix F
authors.initials: FF
authors.lastname: Cruz-Sanchez
authors.forename: Charles
authors.initials: C
authors.lastname: Duyckaerts
authors.forename: Ian R A
authors.initials: IR
authors.lastname: Mackenzie
authors.forename: Robert H
authors.initials: RH
authors.lastname: Perry
authors.forename: Kari
authors.initials: K
authors.lastname: Skullerud
authors.forename: Hedeaki
authors.initials: H
authors.lastname: Yokoo
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Cairns
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism* / Q000473:pathology; D045586:Intranuclear Inclusion Bodies / Q000473:pathology; D008297:Male; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000473:pathology; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000145:classification / Q000378:metabolism / Q000473:pathology; D034702:RNA-Binding Protein FUS / Q000378:metabolism*; D012720:Severity of Illness Index; D013702:Temporal Lobe / Q000378:metabolism / Q000473:pathology*; D055815:Young Adult
chemical_list: D034702:RNA-Binding Protein FUS