Tau-positive glial cytoplasmic granules in multiple system atrophy

Multiple system atrophy (MSA) is a sporadic neurodegenerative disease that is pathologically characterized by the filamentous aggregation of alpha-synuclein. We report a case of MSA showing unusual neuropathological findings and review six autopsied cases of MSA. The patient progressively developed parkinsonism and ataxia for the 9 years prior to her death at the age of 72 years. Neuropathological examinations revealed neuronal loss restricted to the olivopontocerebellar and striatonigral region, which was more severe in the putamen. Staining with anti-alpha-synuclein antibody demonstrated widespread occurrence of glial cytoplasmic inclusions, which mainly accumulated in oligodendroglial cells and corresponded closely to the degree of disease progression. In addition, tau-positive granules were detected within the glial cytoplasm in the neurodegenerative region, which was especially prominent in the putamen and internal capsule. Tau accumulation was also clearly recognized by staining with specific antibodies against three-repeat or four-repeat tau. The glia that demonstrated deposition of tau-positive granules were distinguished from alpha-synuclein-positive oligodendroglia by double immunohistochemical staining. These characteristic glial accumulations of tau were also present in all six cases of MSA. These results indicate that tau-positive granules in glia are common findings in MSA and that tau aggregation might be another pathway to neurodegeneration in MSA.