This scientific commentary refers to ‘Expanding the spectrum of neuronal pathology in multiple system atrophy’, by Cykowski et al. (doi:10.1093/brain/awv114). Multiple system atrophy has long been known to affect different populations of nerve cells in the brain, most often across multiple neural systems—hence the name. The degeneration of distinct but overlapping sets of neurons gives rise to what used to be thought of as three separate clinicopathological disorders—olivopontocerebellar atrophy, striatonigral degeneration and Shy-Drager syndrome—but is now recognized as two main subtypes: a parkinsonian subtype with striatal and nigral degeneration (MSA-P) and a cerebellar subtype with additional pontocerebellar degeneration (MSA-C) (Fanciulli and Wenning, 2015). Both subtypes feature autonomic dysfunction, with associated degeneration in a distributed network of autonomic brain regions (Fanciulli and Wenning, 2015). The most numerous and widespread pathology observed in the brains of such patients is fibrillar oligodendroglial cytoplasmic inclusions (GCI) (Papp and Lantos, 1994), largely composed of the neuronal protein α-synuclein (Gai et al. , 1998). In this regard, multiple system atrophy has been considered unique among neurodegenerative diseases in that it is dominated by proteinaceous inclusion pathology in the myelinating oligodendrocyte rather than in neurons. In this issue of Brain , Cykowski and co-workers assess the neuronal pathologies associated with multiple system atrophy, and conclude that they are more numerous and widespread than previously thought, and likely to have an important role in disease pathophysiology. Widespread neuronal inclusion pathologies have long been acknowledged in multiple system atrophy (Fig. 1A–C); however, their lower numbers and morphological diversity compared to GCIs (Papp and Lantos, 1994) has led to their virtual obscurity over the years. In fact, most studies have disregarded the neuronal inclusion pathology and focused instead on the role of GCIs in various aspects of the disease process. GCIs dominate white matter tracts in multiple …