Alzheimer's disease pathology concomitant with memory impairment in late‐onset multiple system atrophy
Alzheimer's disease pathology concomitant with memory impairment in late‐onset multiple system atrophy
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晚发性多系统萎缩中阿尔茨海默氏病病理学伴随记忆障碍
DOI：
10.1111/nan.12878
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发表时间：
2023
影响因子：
5
通讯作者：
Wakabayashi Koichi
中科院分区：
文献类型：
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作者：
Miki Yasuo;Bettencourt Conceicao;Jaunmuktane Zane;Holton Janice L.;Warner Thomas T.;Wakabayashi Koichi
多系统萎缩症（MSA）的病理特征是受累区域的少突胶质细胞（胶质细胞胞质内含物）和神经元[神经元胞质内含物（NCI）]中异常α-突触核蛋白的积聚。除了帕金森综合征、小脑性共济失调和自主神经功能障碍外，MSA患者还可能出现比以前想象的更广泛的症状，包括认知障碍。我们调查了148例病理证实的MSA患者，他们在2002年至2018年期间被转诊到皇后广场脑库（QSBB）。这些患者中有30例（20%）在生活中表现出认知障碍（额叶皮质下功能障碍和/或记忆障碍）[1]。在这些患者中，18例患者的记忆障碍程度为轻度至中度。此外，病理学检查显示，有记忆障碍的MSA患者海马中的NCI比没有记忆障碍的患者多[1]。我们使用人α-突触核蛋白诱导的MSA小鼠模型和伴或不伴记忆障碍的人MSA病例进一步研究了MSA中记忆障碍的机制[2]。我们发现海马中的α-突触核蛋白寡聚体引起突触功能障碍，导致MSA中记忆障碍的发展[1，2]。
Dear Sir, Multiple system atrophy (MSA) is characterized pathologically by the accumulation of abnormal α-synuclein in oligodendrocytes (glial cytoplasmic inclusions) and neurons [neuronal cytoplasmic inclusions (NCIs)] in affected regions. Patients with MSA can develop a wider array of symptoms than thought previously–including cognitive impairment–in addition to parkinsonism, cerebellar ataxia and autonomic dysfunction. We investigated 148 patients with pathologically proven MSA, who were referred to Queen Square Brain Bank (QSBB) between 2002 and 2018. Thirty of these patients (20%) had manifested cognitive impairment (frontal subcortical dysfunction and/or memory impairment) during life [1]. Among those patients, the degree of memory impairment had been mild to moderate in 18. In addition, pathological examinations had revealed more NCIs in the hippocampus in MSA patients with memory impairment than in those without [1]. We further investigated the mechanism of memory impairment in MSA using a human α-synuclein-inducible MSA mouse model and human MSA cases with or without memory impairment [2]. We found that α-synuclein oligomers in the hippocampus caused synaptic dysfunction, leading to the development of memory impairment in MSA [1, 2].
DOI：
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发表时间：
2009
期刊：
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影响因子：
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作者：
Norihiro Takei;A. Miyashita;Tamao Tsukie;H. Arai;T. Asada;M. Imagawa;M. Shoji;S. Higuchi;Hideo Kimura;H. Takahashi;S. Tsuji;R. Kuwano
通讯作者：
Norihiro Takei;A. Miyashita;Tamao Tsukie;H. Arai;T. Asada;M. Imagawa;M. Shoji;S. Higuchi;Hideo Kimura;H. Takahashi;S. Tsuji;R. Kuwano
DOI：
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发表时间：
2022
期刊：
影响因子：
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作者：
Yasuo Miki;Kunikazu Tanji;Mari Tada;Fumiaki Mori;Helen Ling;Akiyoshi Kakita;Janice L Holton;Thomas T Warner;Koichi Wakabayashi
通讯作者：
Koichi Wakabayashi