Reciprocal accumulation of β-synuclein in α-synuclein lesions in multiple system atrophy

α-Synuclein is a major component of neuronal and glial cytoplasmic inclusions in multiple system atrophy (MSA), one of the α-synucleinopathies. Recent studies have shown that β-synuclein, a homolog of α-synuclein, inhibits α-synuclein aggregation in vitro. We immunohistochemically examined the MSA brain, using specific antibodies against α-synuclein and β-synuclein. α-synuclein-positive filamentous aggregates were frequently found in neurons in the pontine and inferior olivary nuclei. No abnormal accumulation of α-synuclein was noted in Purkinje cells. In contrast, β-synuclein accumulation occurred extensively in Purkinje cells, and only minimally in pontine and olivary neurons. Thus, neuronal α-synuclein inclusions appear to occur only rarely in neurons in which β-synuclein accumulates. These findings support the possibility that β-synuclein is a negative regulator of α-synuclein aggregation.