title: Accumulation of phosphorylated TDP-43 in the CNS of a patient with Cockayne syndrome.
abstract: Here, we report a case of Cockayne syndrome (CS) in a Japanese man who displayed a unique pathology of phosphorylated trans-activation response (TAR) DNA-binding protein 43 (pTDP-43) with abundant Rosenthal fibers. Many round pTDP-43-positive structures were detected throughout the CNS; however, most of them were located in two regions that also exhibited neuronal depletion: the cerebellar cortex and the inferior olivary nucleus. To a lesser extent, these aggregates were also present in the cerebellar white matter, around the subependymal regions in the brain stem, and in the spinal cord. Intraneuronal pTDP-43 inclusions were only observed in a small number of neurons in the inferior olivary nucleus. Double-label immunofluorescence revealed that many of the aggregates were localized to astrocytes. The observed distribution and the morphology of the pTDP-43-positive structures were unique and have not yet been reported. Therefore, a pTDP-43-related pathology may be implicated in CS as well as in other neurodegenerative diseases such as frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Whether the pathology of these diseases reflects a primary neurodegenerative process or a secondary reaction is not known.
authors.affiliation: Department of Neurology, Gunma University Graduate School of Medicine, Maebashi, Japan; Department of Neurology, Hanna-Sawarabi Ryoikuen, Takasaki, Gunma, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sakurai
authors.forename: Kouki
authors.initials: K
authors.lastname: Makioka
authors.forename: Toshio
authors.initials: T
authors.lastname: Fukuda
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Takatama
authors.forename: Koichi
authors.initials: K
authors.lastname: Okamoto
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D003057:Cockayne Syndrome / Q000378:metabolism* / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism / Q000473:pathology; D008297:Male; D010766:Phosphorylation; D057177:TDP-43 Proteinopathies / Q000378:metabolism* / Q000473:pathology*; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins
keywords: Cockayne syndrome; Rosenthal fiber; TDP-43; astrocyte; immunohistochemistry