Reciprocal accumulation of beta-synuclein in alpha-synuclein lesions in multiple system atrophy.

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