Introduction: It is unclear whether tau-positive granular glial pathology is a characteristic feature of MSA. We aimed to analyse the prevalence and significance of tau-positive granular glial pathology in MSA.

Methods: Fourteen MSA cases were clinicopathologically investigated, focusing on tau-positive granular glial pathology in the frontal and temporal white matter and putamen.

Results: In five MSA cases, the temporal white matter showed AT8-positive granular glial pathology; this pathology was detected in the frontal white matter in three cases. AT8-positive granular glia in the white matter were associated with long disease duration with long-term tube feeding and/or long-term tracheotomy. Alpha-synuclein-positive glial cytoplasmic inclusion intensity was not associated with AT8-positive granular glial pathology. The tau isoform of AT8-positive granular glia in the cerebral white matter exhibited three-repeat, not four-repeat, tau. Ten MSA patients showed tau-positive granular glial pathology in the putamen; the tau isoform was predominantly three-repeat tau and four-repeat tau in cases with disease duration ≥13 years and < 13 years, respectively.

Conclusions: Tau-positive granular glia in the putamen is a characteristic pathological feature of MSA. Tau-positive granular glia appear in the cerebral white matter in MSA patients and are associated with long disease duration with long-term tube feeding and/or long-term tracheotomy.