α -Synuclein coaggregation in familial amyotrophic lateral sclerosis with SOD1 gene mutation

Summary Immunohistochemical studies were performed on postmortem brain and spinal cord from a patient with familial amyotrophic lateral sclerosis characterized by a C111Y mutation in the Cu / Zn superoxide dismutase gene. Clinically, the patient presented with classical amyotrophic lateral sclerosis and died of respiratory failure at age 53 years without ventilator dependence, 4 years after the onset. Pathologically, loss of motor neurons was more extensive than upper motor neurons. Lower motor neurons developed massive intracellular cytoplasmic neuronal inclusions, which were immunoreactive for Cu/Zn superoxide dismutase and phosphorylated α -synuclein, often colocalized. The inclusions were TAR DNA-binding protein 43 negative. The clinicopathologic significance of coaggregation of α -synuclein and Cu/Zn superoxide dismutase protein, a novel finding in neurodegenerative disorders, needs further investigation.