Novel immunolocalization of alpha-synuclein in human muscle of inclusion-body myositis, regenerating and necrotic muscle fibers, and at neuromuscularjunctions

alpha-synuclein (alpha-syn) is an important component of neuronal and glial inclusions in brains of patients with several neurodegenerative disorders. Sporadic inclusion-body myositis (s-IBM) is the most common progressive mu scle disease of older patients. Its muscle phenotype shows several similari ties with Alzheimer disease brain. a distinct feature of s-IBM pathology is specific vacuolar degeneration of muscle fibers characterized by intracell ular amyloid inclusions formed by both amyloid-beta (A beta) and paired-hel ical filaments composed of phosphorylated tau. We immunostained alpha-syn i n muscle biopsies of s-IBM, disease-control, and normal patients. Approxima tely 60% of A beta-positive vacuolated muscle fibers (VMF) contained well-d efined inclusions immunoreactive with antibodies against alpha-syn. In thos e fibers, alpha-syn co-localized with A beta, both by light microscopy, and ultrastructurally. Paired-helical filaments did not contain alpha-syn immu noreactivity. In all muscle biopsies, alpha-syn was strongly immunoreactive at the postsynaptic region of the neuromuscular junctions, alpha-syn immun oreactivity also occurred diffusely in regenerating and necrotic muscle fib ers. In cultured human muscle fibers, alpha-syn and its mRNA were expressed by immunocytochemistry, immunoblots, and Northern blots. Our study provide s the first demonstration that alpha-syn participates in normal and patholo gic processes of human muscle. Therefore, its function is not exclusive to the brain and neurodegenerative diseases.