title: An autopsy case of familial amyotrophic lateral sclerosis with a TARDBP Q343R mutation.
abstract: We describe a Japanese autopsy case of familial amyotrophic lateral sclerosis (FALS) with a TARDBP Q343R mutation. This male patient developed dysarthria at the age of 52 years, and bulbar symptoms progressed, with weakness and atrophy in the extremities. His mental status was normal, but he became bedridden, received artificial respiratory support at 54 years of age, and gradually acquired a locked-in state and died at 58 years of age. Microscopically, marked diffuse myelin pallor was observed in the anterolateral columns of the spinal cord. The remaining anterior horn cells contained Bunina bodies and phosphorylation-dependent transactivation response DNA-binding protein of 43 kDa (pTDP-43)-positive neuronal cytoplasmic inclusions (NCIs). Glial cytoplasmic inclusions (GCIs) were also observed. The number of ubiquitin- and p62-positive inclusions was markedly lower than that of pTDP-43-positive inclusions. NCIs and many fine dot-like pTDP-43-positive granules in the neuropil were mainly seen in the temporal and motor cortices, and striatum. NCIs were rare in hippocampal granular cells. Immunoblotting of samples from the cerebral cortex using an anti-pTDP-43 antibody was slightly different from previous TDP-43 pathological subtypes.
authors.affiliation: Department of Neurology, Geriatrics Research Institute and Hospital, Maebashi, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Okamoto
authors.affiliation: Department of Neurology, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Fujita
authors.affiliation: Department of Neurology, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Hoshino
authors.affiliation: Department of Internal Medicine, Kiboukan Hospital, Takasaki, Japan.
authors.forename: Yuhji
authors.initials: Y
authors.lastname: Tamura
authors.affiliation: Department of Histopathology and Cytopathology, Gunma University Graduate School of Health Sciences, Maebashi, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Fukuda
authors.affiliation: Department of Neuropathology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Hasegawa
authors.affiliation: Department of Internal Medicine, Geriatrics Research Institute and Hospital, Maebashi, Japan.
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Takatama
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000473:pathology; D000870:Anterior Horn Cells / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000235:genetics*; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D002479:Inclusion Bodies / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009474:Neurons / Q000473:pathology; D013116:Spinal Cord / Q000473:pathology*
chemical_list: D004268:DNA-Binding Proteins; C000598624:TARDBP protein, human
keywords: TARDBP Q343R mutation; TDP-43; amyotrophic lateral sclerosis; p62; pathology