Co-localization of α-synuclein and phosphorylated tau in neuronal and glial cytoplasmic inclusions in a patient with multiple system atrophy of ... View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2001-03

AUTHORS

Yue-Shan Piao, Shintaro Hayashi, Masato Hasegawa, Koichi Wakabayashi, Mitsunori Yamada, Makoto Yoshimoto, Atsushi Ishikawa, Takeshi Iwatsubo, Hitoshi Takahashi

ABSTRACT

Neuronal and glial cytoplasmic inclusions (NCIs and GCIs), which contain alpha-synuclein as a major component, are characteristic cytopathological features of multiple system atrophy (MSA). We report MSA of 19 years' duration in a 73-year-old woman. Her initial symptom was parkinsonism, with dementia appearing about 8 years later. Postmortem examination showed marked atrophy of the frontal and temporal white matter and limbic system, in addition to the pathology typical of MSA. In the limbic system, severe neuronal loss and astrocytosis were observed, and the remaining neurons often had lightly eosinophilic, spherical cytoplasmic inclusions. Interestingly, a double-labeling immunofluorescence study revealed that the NCIs in the dentate gyrus and amygdaloid nucleus, and the GCIs in the frontal and temporal white matter often expressed both alpha-synuclein NACP-5 and phosphorylated tau AT8 epitopes. Double-immunolabeling electron microscopy of the NCIs in the dentate gyrus and the GCIs in the temporal white matter clearly revealed labeling of their constituent granule-associated filaments with NACP-5, and some of them were also labeled with AT8. These findings strongly suggested that some alpha-synuclein filaments were decorated with phosphorylated tau without formation of fibrils such as paired helical filaments. Immunoblotting of sarkosyl-insoluble tau indicated that the accumulated tau consisted mainly of four-repeat tau isoforms of 383 amino acids and 412 amino acids. We consider that the limbic system can be a major site of neurodegeneration in MSA of long duration. The mechanisms of such abnormal tau accumulation in the NCIs and GCIs are unknown. More... »

PAGES

285-293

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s004010000292

DOI

http://dx.doi.org/10.1007/s004010000292

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1074800816

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/11307630


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