The α-synuclein pathology of multiple system atrophy. Glial cytoplasmic inclusions in several brain regions define multiple system atrophy. Similar inclusions are also present in the nuclei of some glial cells, as well as in the cytoplasm and nuclei of some nerve cells, and in nerve cell processes. Inclusions are shown here at light (a-f) and electron microscopic (g-j) levels, labelled by α-synuclein antibodies. (a-d) α-Synuclein-immunoreactive oligodendrocytes and nerve cells in white matter of pons (a,b,d) and cerebellum (c,e,f). α-Synuclein-immunoreactive oligodendrocytes and nerve cells in grey matter of pons (e) and frontal cortex (f). Arrows identify the characteristic lesions: cytoplasmic, oligodendroglial inclusions (a,f), cytoplasmic nerve cell inclusions (b), nuclear oligodendroglial inclusions (c), neuropil threads (d) and nuclear nerve cell inclusions (e). Scale bar, 33μm in (e) and 50μm in (f). (g-j), Isolated filaments from the frontal cortex and cerebellum of patients with multiple system atrophy are decorated by antibodies specific for the carboxy-terminal (g,h) and amino-terminal (i,j) regions of α-synuclein. The gold particles conjugated to the secondary antibody appear as black dots. Note the uniform decoration in (g,h) and the labelling of only one filament end in (i,j). A twisted filament is shown in (g), whereas (h) shows a straight filament. Scale bar, 100 nm. From Goedert [205].