Accumulation of phosphorylated α-synuclein in the brain and peripheral ganglia of patients with multiple system atrophy

被引:94
作者
Nishie, M
Mori, F
Fujiwara, H
Hasegawa, M
Yoshimoto, M
Iwatsubo, T
Takahashi, H
Wakabayashi, K
机构
[1] Hirosaki Univ, Sch Med, Inst Brain Sci, Dept Neuropathol, Hirosaki, Aomori 0368562, Japan
[2] Univ Tokyo, Grad Sch Pharmaceut Sci, Dept Neuropathol & Neurosci, Tokyo, Japan
[3] Tokyo Metropolitan Org Med Res, Tokyo Inst Psychiat, Dept Mol Neurobiol, Tokyo, Japan
[4] Taisho Pharmaceut, Med Res Labs, Mol Biol Lab, Saitama, Japan
[5] Niigata Univ, Brain Res Inst, Dept Pathol, Niigata, Japan
关键词
multiple system atrophy; alpha-synucleinopathy; neuronal cytoplasmic inclusions; neuropil threads; phosphorylation;
D O I
10.1007/s00401-003-0811-1
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
We immunohistochemically examined the brain and peripheral sympathetic ganglia from eight patients with multiple system atrophy (MSA), using an antibody specific for phosphorylated alpha-synuclein (anti-PSer129). Phosphorylated alpha-synuclein was deposited in five cellular locations: oligodendroglial cytoplasm and nucleus, and neuronal cytoplasm, processes and nucleus. Many neuronal cytoplasmic inclusions (NCIs) were found in the pontine and inferior olivary nuclei and, to a lesser extent, in the substantia nigra, locus ceruleus, and neocortical and hippocampal neurons. NCIs were also found in the sympathetic ganglia in two out of the eight cases. Moreover, anti-PSer129 immunohistochemistry revealed extensive neuropil pathology; swollen neurites were abundant in the pontine nucleus, delicate neurites were observed in the deeper layers of the cerebral cortex and thalamus, and neuropil threads and dot-like structures were distributed in the basal ganglia and brainstem. Diffuse neuronal cytoplasmic staining (pre-NCI) was frequently found in the pontine and inferior olivary nuclei. Thus, the widespread accumulation of phosphorylated alpha-synuclein in both glial and neuronal cells is a pathological feature in patients suffering from MSA.
引用
收藏
页码:292 / 298
页数:7
相关论文
共 38 条
[31]   Phosphorylation of α-synuclein characteristic of synucleinopathy lesions is recapitulated in α-synuclein transgenic Drosophila [J].
Takahashi, M ;
Kanuka, H ;
Fujiwara, H ;
Koyama, A ;
Hasegawa, M ;
Miura, M ;
Iwatsubo, T .
NEUROSCIENCE LETTERS, 2003, 336 (03) :155-158
[32]   Expression of α-synuclein in a human glioma cell line and its up-regulation by interleukin-1β [J].
Tanji, K ;
Imaizumi, T ;
Yoshida, H ;
Mori, F ;
Yoshimoto, M ;
Satoh, K ;
Wakabayashi, K .
NEUROREPORT, 2001, 12 (09) :1909-1912
[33]   Glial cytoplasmic inclusions in white matter oligodendrocytes of multiple system atrophy brains contain insoluble α-synuclein [J].
Tu, PH ;
Galvin, JE ;
Baba, M ;
Giasson, B ;
Tomita, T ;
Leight, S ;
Nakajo, S ;
Iwatsubo, T ;
Trojanowski, JQ ;
Lee, VMY .
ANNALS OF NEUROLOGY, 1998, 44 (03) :415-422
[34]   Accumulation of α-synuclein/NACP is a cytopathological feature common to Lewy body disease and multiple system atrophy [J].
Wakabayashi, K ;
Hayashi, S ;
Kakita, A ;
Yamada, M ;
Toyoshima, Y ;
Yoshimoto, M ;
Takahashi, H .
ACTA NEUROPATHOLOGICA, 1998, 96 (05) :445-452
[35]  
Wakabayashi K, 1999, NEUROPATH APPL NEURO, V25, P363
[36]   CLINICAL-FEATURES AND NATURAL-HISTORY OF MULTIPLE SYSTEM ATROPHY - AN ANALYSIS OF 100 CASES [J].
WENNING, GK ;
BENSHLOMO, Y ;
MAGALHAES, M ;
DANIEL, SE ;
QUINN, NP .
BRAIN, 1994, 117 :835-845
[37]   α-synuclein inclusions in amygdala in the brains of patients with the Parkinsonism-dementia complex of Guam [J].
Yamazaki, M ;
Arai, Y ;
Baba, M ;
Iwatsubo, T ;
Mori, O ;
Katayama, Y ;
Oyanagi, K .
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 2000, 59 (07) :585-591
[38]   NACP/α-synuclein immunoreactivity in diffuse neurofibrillary tangles with calcification (DNTC) [J].
Yokota, O ;
Terada, S ;
Ishizu, H ;
Tsuchiya, K ;
Kitamura, Y ;
Ikeda, K ;
Uéda, K ;
Kuroda, S .
ACTA NEUROPATHOLOGICA, 2002, 104 (04) :333-341