α-Synuclein pathology in the amyotrophic lateral sclerosis/parkinsonism dementia complex in the Kii Peninsula, Japan.
α-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 α-synuclein-positive structures including neuronal cytoplasmic inclusions, dystrophic neurites, and glial cytoplasmic inclusions were found in all ALS/PDC cases. There were phosphorylated α-synuclein-positive neurons in 8 cases (80%), and the amygdala was most severely affected. Phosphorylated α-synuclein was distributed mainly in the limbic system and brainstem; tau pathology was more prevalent than α-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, α-synuclein pathology was more predominant than tau pathology in only 1 or 2 patients. Phosphorylated α-synuclein- positive structures were not found in the molecular layer of the cerebellum. Phosphorylated α-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 α-synuclein-immunoreactive bands that were ubiquitinated. These results suggest that interaction between tau and α-synuclein be involved in the pathogenesis of Kii ALS/PDC.
Department of Neurology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan. kokubo-y@clin.medic.mie-u.ac.jp
Yasumasa
Y
Kokubo
Akira
A
Taniguchi
Masato
M
Hasegawa
Yuma
Y
Hayakawa
Satoru
S
Morimoto
Misao
M
Yoneda
Yoshihumi
Y
Hirokawa
Taizo
T
Shiraishi
Yuko
Y
Saito
Shigeo
S
Murayama
Shigeki
S
Kuzuhara
D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000150:complications / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000473:pathology; D003704:Dementia / Q000150:complications / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D002479:Inclusion Bodies / Q000473:pathology; D007564:Japan; D008297:Male; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000473:pathology; D009474:Neurons / Q000473:pathology; D020734:Parkinsonian Disorders / Q000150:complications / Q000378:metabolism / Q000473:pathology; D051844:alpha-Synuclein / Q000378:metabolism*
D051844:alpha-Synuclein