Proteomic analysis of human hippocampal subfields provides new insights into the pathogenesis of Alzheimer's disease and the role of glial cells.
Proteomic analysis of human hippocampal subfields provides new insights into the pathogenesis of Alzheimer's disease and the role of glial cells.
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人类海马亚区的蛋白质组学分析为阿尔茨海默病的发病机制和神经胶质细胞的作用提供了新的见解
DOI：
10.1111/bpa.13047
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发表时间：
2022-07
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影响因子：
--
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中科院分区：
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海马体和内嗅皮质（EC）是最早受影响的区域，被认为与阿尔茨海默病（AD）的早期记忆丧失有关。海马体由不同种类的子区组成，在阿尔茨海默病发病过程中受到不同顺序和不同程度的影响。在这项研究中，我们对来自中国人脑库的人死后标本的海马亚区和EC区进行了全面的蛋白质组学分析。生物信息学分析确定了与星形胶质细胞相关的区域一致差异表达蛋白（DEPs），以及与少突胶质细胞和髓鞘相关的区域特异性差异表达蛋白（DEPs）。进一步分析表明，区域一致性dep作为区域特异性dep的连接。此外，在区域一致的DEPs中，S100A10（保护性星形胶质细胞的标志）的表达水平在衰老和AD患者中都有所增加。免疫组织化学分析证实，在AD患者的所有海马亚区和EC区，S100A10阳性星形胶质细胞数量增加。双免疫荧光结果进一步显示，S100A10阳性星形胶质细胞在AD患者体内含有凋亡神经元碎片，提示S100A10阳性星形胶质细胞可能通过吞噬凋亡神经元来保护大脑。在区域特异性DEPs中，蛋白质组显示AD患者CA1、CA3和EC区域的少突胶质细胞和髓磷脂标志物特异性减少。免疫组化分析证实EC区髓磷脂缺失。总之，这些结果突出了神经胶质细胞在AD中的作用，并为AD的发病机制和潜在的治疗策略提供了新的见解。在这项研究中，我们对来自中国人脑库的人死后标本的海马亚区和内嗅皮层（EC）区域进行了全面的蛋白质组学分析。综合蛋白质组学、病理学和组织化学结果强调了神经胶质细胞在阿尔茨海默病（AD）发病机制中的作用。
The hippocampus and entorhinal cortex (EC), the earliest affected areas, are considered relative to early memory loss in Alzheimer's disease (AD). The hippocampus is composed of heterogeneous subfields that are affected in a different order and varying degrees during AD pathogenesis. In this study, we conducted a comprehensive proteomic analysis of the hippocampal subfields and EC region in human postmortem specimens obtained from the Chinese human brain bank. Bioinformatics analysis identified region‐consistent differentially expressed proteins (DEPs) which associated with astrocytes, and region‐specific DEPs which associated with oligodendrocytes and the myelin sheath. Further analysis illuminated that the region‐consistent DEPs functioned as connection of region‐specific DEPs. Moreover, in region‐consistent DEPs, the expression level of S100A10, a marker of protective astrocytes, was increased in both aging and AD patients. Immunohistochemical analysis confirmed an increase in the number of S100A10‐positive astrocytes in all hippocampal subfields and the EC region of AD patients. Dual immunofluorescence results further showed that S100A10‐positive astrocytes contained apoptotic neuron debris in AD patients, suggesting that S100A10‐positive astrocytes may protect brain through phagocytosis of apoptotic neurons. In region‐specific DEPs, the proteome showed a specific reduction of oligodendrocytes and myelin markers in CA1, CA3, and EC regions of AD patients. Immunohistochemical analysis confirmed the loss of myelin in EC region. Above all, these results highlight the role of the glial cells in AD and provide new insights into the pathogenesis of AD and potential therapeutic strategies. In this study, we conducted a comprehensive proteomic analysis of the hippocampal subfields and entorhinal cortex (EC) region in human postmortem specimens obtained from the Chinese human brain bank. Integrated proteomics, pathology, and histochemistry results highlight the role of glial cells in Alzheimer's disease (AD) pathogenesis.
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影响因子：
3.3
作者：
Di Domenico, Fabio;Sultana, Rukhsana;Barone, Eugenio;Perluigi, Marzia;Cini, Chiara;Mancuso, Cesare;Cai, Jian;Pierce, William M.;Butterfield, D. Allan
通讯作者：
Butterfield, D. Allan
影响因子：
16.2
作者：
Bai, Bing;Wang, Xusheng;Peng, Junmin
通讯作者：
Peng, Junmin
影响因子：
6
作者：
Desai, Maya K.;Mastrangelo, Michael A.;Bowers, William J.
通讯作者：
Bowers, William J.
影响因子：
14
作者：
通讯作者：
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影响因子：
14
作者：
Elahi, Fanny M.;Casaletto, Kaitlin B.;Kramer, Joel H.
通讯作者：
Kramer, Joel H.