Pathological changes in the cerebellum of patients with multiple system atrophy and Parkinson's disease—a stereological study

Abstract Multiple system atrophy (MSA) and Parkinson's disease (PD) are synucleinopathies characterized by aggregation of α‐synuclein in brain cells. Recent studies have shown that morphological changes in terms of cerebral nerve cell loss and increase in glia cell numbers, the degree of brain atrophy and molecular and epidemiological findings are more severe in MSA than PD. In the present study, we performed a stereological comparison of cerebellar volumes, granule and Purkinje cells in 13 patients diagnosed with MSA [8 MSA‐P (striatonigral subtype) and 5 MSA‐C (olivopontocerebellar subtype)], 12 PD patients, and 15 age‐matched control subjects. Only brains from MSA‐C patients showed a reduction in the total number of Purkinje cells (anterior lobe) whereas both MSA‐P and MSA‐C patients had reduced Purkinje cell volumes (perikaryons and nuclei volume). The cerebellum of both diseases showed a reduction in the white matter volume compared to controls. The number of granule cells was unaffected in both diseases. Analyses of cell type‐specific mRNA expression supported our structural data. This study of the cerebellum is in line with previous findings in the cerebrum and demonstrates that the degree of morphological changes is more pronounced in MSA‐C than MSA‐P and PD. Further, our results support an explicit involvement of cerebellar Purkinje cells and white matter connectivity in MSA‐C > MSA‐P and points to the potential importance of white matter alterations in PD pathology.