Type-specific evolution of amyloid plaque and angiopathy in APPsw mice
Type-specific evolution of amyloid plaque and angiopathy in APPsw mice
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DOI：
10.1016/j.neulet.2005.10.087
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发表时间：
2006-02
影响因子：
2.5
通讯作者：
Y. Harigaya;Y. Tomidokoro;M. Ikeda;A. Sasaki;T. Kawarabayashi;E. Matsubara;M. Kanai;T. Saido;S. Younkin;M. Shoji
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文献类型：
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作者：
Y. Harigaya;Y. Tomidokoro;M. Ikeda;A. Sasaki;T. Kawarabayashi;E. Matsubara;M. Kanai;T. Saido;S. Younkin;M. Shoji
为了阐明Aβ沉积是如何在大脑中开始的，我们检查了APPsw小鼠中老年斑和淀粉样血管病的早期到晚期。在小鼠脑中观察到所有类型的人类老年斑。在7-8个月大的小鼠大脑皮层中首先出现早期形式的核心斑块。然后出现淀粉样血管病，随后出现由Aβ1-42组成的弥漫性斑块。Aβ N端的修饰是晚期现象。核心斑块的早期形式由中心Aβ1-40淀粉样蛋白核心、周围无定形Aβ1-42沉积物和一些外周细胞中Aβ1-42的积聚组成。这些细胞被整合到淀粉样蛋白核心中，这些斑块发展成由Aβ1-40和Aβ1-42组成的大核心斑块。核心斑块的大小和数量随着年龄的增长而增加。这些发现表明核心斑块和弥漫性斑块的不同演变路径，并表明存在一种途径，该途径始于Aβ1-42的细胞内积累，并导致人脑组织中经典斑块的发展。
To clarify how Aβ deposits start in the brain, we examined the early to late stages of senile plaques and amyloid angiopathy in APPsw mice. All types of human senile plaques were observed in the mouse brains. The premature forms of cored plaques appeared first in the cerebral cortex of mice at 7–8 months old. Then, amyloid angiopathy emerged, followed by diffuse plaques consisting of Aβ1–42. Modifications of the N-terminus of Aβ were late phase phenomena. The premature forms of cored plaques were composed of central Aβ1–40 amyloid cores, surrounding amorphous Aβ1–42 deposits, and accumulation of Aβ1–42 in some peripheral cells. These cells were incorporated in amyloid cores, and these plaques developed to large cored plaques composed of Aβ1–40 and Aβ1–42. The size and number of cored plaques were increased with age. These findings indicate different evolution paths for cored plaques and diffuse plaques, and suggest the presence of a pathway that initiates with the intracellular accumulation of Aβ1–42 and leads to the development of classic plaques in human brain tissues.