Accumulation of phosphorylated α-synuclein in subpial and periventricular astrocytes in multiple system atrophy of long duration.
The histological hallmark of multiple system atrophy (MSA) is accumulation of phosphorylated α-synuclein in oligodendrocytes. However, it is uncertain whether phosphorylated α-synuclein accumulates in astrocytes of MSA patients. We immunohistochemically examined the frontal and temporal lobes, basal ganglia, cerebellum, brainstem and spinal cord of patients with MSA (n = 15) and Lewy body disease (n = 20), and also in control subjects (n = 20). Accumulation of abnormally phosphorylated and aggregated α-synuclein was found in subpial and periventricular astrocytes in six of the 15 patients with MSA (40%). The structures were confined to the subpial surface of the ventro-lateral part of the spinal cord and brainstem, as well as the subependymal region of the lateral ventricles. They were not visualized by Gallyas-Braak staining, and were immunonegative for ubiquitin and p62. Immunoelectron microscopy revealed that the phosphorylated α-synuclein-immunoreactive structures in astrocytes were non-fibrillar and associated with granular and vesicular structures. The extent of phosphorylated α-synuclein-immunoreactive astrocytes was correlated with disease duration. No such structures were found in Lewy body disease or controls. Accumulation of phosphorylated α-synuclein can occur in subpial and periventricular astrocytes in patients with MSA, especially in those with a long disease duration.
Department of Neuropathology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki.|Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Science, Kanazawa.
Keiko
K
Nakamura
Department of Neuropathology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki.
Fumiaki
F
Mori
Departments of Neurology, Aomori.
Tomoya
T
Kon
Department of Neuropathology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki.
Kunikazu
K
Tanji
Department of Neuropathology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki.
Yasuo
Y
Miki
Departments of Neurology, Aomori.
Masahiko
M
Tomiyama
Pathology, Aomori Prefectural Central Hospital, Aomori.
Hidekachi
H
Kurotaki
Departments of Pathology, Niigata, Japan.
Yasuko
Y
Toyoshima
Pathological Neuroscience, Brain Research Institute, University of Niigata, Niigata, Japan.
Akiyoshi
A
Kakita
Departments of Pathology, Niigata, Japan.
Hitoshi
H
Takahashi
Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Science, Kanazawa.
Masahito
M
Yamada
Department of Neuropathology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki.
Koichi
K
Wakabayashi
D000368:Aged; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology*; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000473:pathology; D020961:Lewy Body Disease / Q000473:pathology; D008297:Male; D016253:Microscopy, Immunoelectron; D008875:Middle Aged; D019578:Multiple System Atrophy / Q000378:metabolism / Q000473:pathology*; D010766:Phosphorylation; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D051844:alpha-Synuclein / Q000378:metabolism*
C497604:SNCA protein, human; D051844:alpha-Synuclein
astrocyte; multiple system atrophy; subpial surface; ultrastructure; α-synuclein