Co-localization of alpha-synuclein and phosphorylated tan in neuronal and glial cytoplasmic inclusions in a patient with multiple system atrophy of long duration

Neuronal and glial cytoplasmic inclusions (NCIs and GCIs), which contain al pha -synuclein as a major component, are characteristic cytopathological fe atures of multiple system atrophy (MSA). We report MSA of 19 years' duratio n in a 73-year-old woman. Her initial symptom was parkinsonism, with dement ia appearing about 8 years later. Postmortem examination showed marked atro phy of the frontal and temporal white matter and limbic system, in addition to the pathology typical of MSA. In the limbic system, severe neuronal los s and astrocytosis were observed, and the remaining neurons often had light ly eosinophilic, spherical cytoplasmic inclusions. Interestingly, a double- labeling immunofluorescence study revealed that the NCIs in the dentate gyr us and amygdaloid nucleus, and the GCIs in the frontal and temporal white m atter often expressed both alpha -synuclein NACP-5 and phosphorylated tau A T8 epitopes. Double-immunolabeling electron microscopy of the NCIs in the d entate gyrus and the GCIs in the temporal white matter clearly revealed lab eling of their constituent granule-associated filaments with NACP-5, and so me of them were also labeled with AT8. These findings strongly suggested th at some alpha -synuclein filaments were decorated with phosphorylated tau w ithout formation of fibrils such as paired helical filaments. Immunoblottin g of sarkosyl-insoluble tau indicated that the accumulated tau consisted ma inly 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 i n MSA of long duration. The mechanisms of such abnormal tau accumulation in the NCIs and GCIs are unknown.