Satoh Jun-Ichi, Kino Yoshihiro, Yanaizu Motoaki, Ishida Tsuyoshi, Saito Yuko
Department of Bioinformatics and Molecular Neuropathology, Meiji Pharmaceutical University, Tokyo, Japan.
Department of Pathology and Laboratory Medicine, Kohnodai Hospital, National Center for Global Health and Medicine, Chiba, Japan.
Intractable Rare Dis Res. 2020 Nov;9(4):217-221. doi: 10.5582/irdr.2020.03080.
By combining genomic data and brain imaging data, a recent study has identified a novel gene named that participates in the formation of amyloid-β (Aβ) plaques and brain atrophy in Alzheimer's disease (AD). encodes a 47-kDa protein designated Aggregatin that accumulates in the center of amyloid plaques and physically interacts with Aβ to facilitate Aβ aggregation. Aggregatin is expressed predominantly in the central nervous system (CNS) and its levels are increased in brains of the patients with AD and in mouse models of AD. However, at present, the precise cell types that express Aggregatin in the human CNS remain unknown. By immunohistochemistry, we studied Aggregatin expression in the frontal lobe of the patients with AD, Nasu-Hakola disease (NHD), and the subjects who died of non-neurological causes (NNC). We identified the clusters of Aggregatin-positive reactive astrocytes distributed widely in the cerebral cortex of most cases examined. In contrast, small numbers of cortical neurons showed variable immunoreactivities for Aggregatin, whereas microglia and oligodendrocytes did not express Aggregatin. Importantly, amyloid plaques were not clearly labelled with anti-Aggregatin antibody. These results suggest that Aggregatin plays a primarily role in generation of reactive astrocytes in the human CNS.
通过整合基因组数据和脑成像数据,最近一项研究鉴定出一个名为 的新基因,它参与阿尔茨海默病(AD)中淀粉样β蛋白(Aβ)斑块的形成和脑萎缩。 编码一种名为聚集素的47 kDa蛋白,该蛋白聚集在淀粉样斑块的中心,并与Aβ发生物理相互作用以促进Aβ聚集。聚集素主要在中枢神经系统(CNS)中表达,在AD患者的大脑和AD小鼠模型中其水平升高。然而,目前在人类CNS中表达聚集素的精确细胞类型仍不清楚。通过免疫组织化学,我们研究了AD患者、那须-哈科拉病(NHD)患者以及死于非神经原因(NNC)的受试者额叶中聚集素的表达。我们发现在大多数检查病例的大脑皮层中广泛分布着聚集素阳性反应性星形胶质细胞簇。相比之下,少数皮层神经元对聚集素显示出可变的免疫反应性,而小胶质细胞和少突胶质细胞不表达聚集素。重要的是,淀粉样斑块未被抗聚集素抗体清晰标记。这些结果表明聚集素在人类CNS中反应性星形胶质细胞的产生中起主要作用。