α-Synuclein Pathology in the Amyotrophic Lateral Sclerosis/Parkinsonism Dementia Complex in the Kii Peninsula, Japan

alpha-Synuclein pathology was examined in the brains and spinal cords of 10 patients with amyotrophic lateral sclerosis (ALS)/parkinsonism-dementia complex (PDC) in the Kii Peninsula, Japan. Various types of phosphorylated alpha-synuclein-positive structures including neuronal cytoplasmic inclusions, dystrophic neurites, and glial cytoplasmic inclusions were found in all ALS/PDC cases. There were phosphorylated alpha-synuclein-positive neurons in 8 cases (80%), and the amygdala was most severely affected. Phosphorylated alpha-synuclein was distributed mainly in the limbic system and brainstem; tau pathology was more prevalent than alpha-synuclein pathology in most affected areas. In the substantia nigra, periaqueductal gray, locus coeruleus, raphe nuclei, dorsal nucleus of the vagus nerve, hypoglossal nucleus or ventral horn, and intermediolateral nucleus of the spinal cord, alpha-synuclein pathology was more predominant than tau pathology in only 1 or 2 patients. Phosphorylated alpha-synuclein-positive structures were not found in the molecular layer of the cerebellum. Phosphorylated alpha-synuclein frequently colocalized with tau in neuron cell bodies, neurites, and glia. Immunoblots of sarkosyl-insoluble fractions extracted from the brain of 1 patient showed a triplet of alpha-synuclein-immunoreactive bands that were ubiquitinated. These results suggest that interaction between tau and alpha-synuclein be involved in the pathogenesis of Kii ALS/PDC.