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Accumulation of phosphorylated TDP ‐43 in the CNS of a patient with C ockayne syndrome
Author(s) -
Sakurai Atsushi,
Makioka Kouki,
Fukuda Toshio,
Takatama Masamitsu,
Okamoto Koichi
Publication year - 2013
Publication title -
neuropathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.701
H-Index - 61
eISSN - 1440-1789
pISSN - 0919-6544
DOI - 10.1111/neup.12038
Subject(s) - cerebellar cortex , subependymal zone , inferior olivary nucleus , cerebellum , nucleus , white matter , biology , pons , chemistry , microbiology and biotechnology , neuroscience , medicine , radiology , magnetic resonance imaging
Here, we report a case of C ockayne syndrome ( CS ) in a J apanese 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.