Accumulation of phosphorylated α‐synuclein in subpial and periventricular astrocytes in multiple system atrophy of long duration

The histological hallmark of multiple system atrophy (MSA) is accumulation of phosphorylated α‐synuclein in oligodendrocytes. However, it is uncertain whether phosphorylated α‐synuclein accumulates in astrocytes of MSA patients. We immunohistochemically examined the frontal and temporal lobes, basal ganglia, cerebellum, brainstem and spinal cord of patients with MSA ( n = 15) and Lewy body disease ( n = 20), and also in control subjects ( n = 20). Accumulation of abnormally phosphorylated and aggregated α‐synuclein was found in subpial and periventricular astrocytes in six of the 15 patients with MSA (40%). The structures were confined to the subpial surface of the ventro‐lateral part of the spinal cord and brainstem, as well as the subependymal region of the lateral ventricles. They were not visualized by Gallyas‐Braak staining, and were immunonegative for ubiquitin and p62. Immunoelectron microscopy revealed that the phosphorylated α‐synuclein‐immunoreactive structures in astrocytes were non‐fibrillar and associated with granular and vesicular structures. The extent of phosphorylated α‐synuclein‐immunoreactive astrocytes was correlated with disease duration. No such structures were found in Lewy body disease or controls. Accumulation of phosphorylated α‐synuclein can occur in subpial and periventricular astrocytes in patients with MSA, especially in those with a long disease duration.