FE65 in Alzheimer's disease - Neuronal distribution and association with neurofibrillary tangles

FE65 in Alzheimer's disease - Neuronal distribution and association with neurofibrillary tangles
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DOI:
10.1016/s0002-9440(10)64113-2
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发表时间:
2001-05-01
影响因子:
6
通讯作者:
Duyckaerts, C
Duyckaerts, C
中科院分区:
医学2区
文献类型:
--
作者:
Delatour, B;Mercken, L;Duyckaerts, C

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FE 65是一种在神经系统中表达的蛋白质,具有结合淀粉样前体蛋白C-末端结构域的能力。这表明FE 65在阿尔茨海默病(AD)的发病机制中发挥作用。本研究旨在查明FE 65免疫反应性的分布在AD过程中是否受到影响,并确定FE 65的共定位程度。与其他已知参与AD的蛋白质。单一的免疫过氧化物酶标记实验,进行了6个散发性AD患者和6个非痴呆年龄匹配的控制,结果表明,所占的体积比例FE 65免疫反应性没有修改的同皮质AD患者。然而,在海马CA 4区,FE 65免疫反应性增加似乎与疾病的严重程度有关。双免疫荧光标记没有显示任何明确的共定位FE 65与淀粉样前体蛋白。FE 65免疫反应性也不存在于P-淀粉样肽的局灶性和弥漫性沉积物中。出乎意料的双标记实验显示FE 65和tau蛋白在细胞内缠结中的共定位。超微结构观察证实,FE 65与成对的螺旋丝有关。
FE65, a protein expressed in the nervous system, has the ability to bind the C-terminal domain of the amyloid precursor protein. This suggests a role for FE65 in the pathogenesis of Alzheimer's disease (AD), The present study mas conducted to find out if the distribution of FE65 immunoreactivity was affected during the course of AD, and to determine the degree of co-localization of FE65 with other proteins known to be involved in AD. Single immunoperoxidase-labeling experiments, conducted on six sporadic AD patients and six nondemented age-matched controls, showed that the proportion of volume occupied by FE65 immunoreactivity was not modified in the isocortex of AD patients. However, in hippocampal area CA4, increased FE65 immunoreactivity seemed to be associated with the severity of the disease. Double-immunofluorescent labeling did not show any clear co-localization of FE65 with the amyloid precursor protein. FE65 immunoreactivity was also absent from focal and diffuse deposits of the P-amyloid peptide. Unexpectedly double labeling experiments showed a co-localization of FE65 and tau proteins in intracellular tangles. Ultrastructural observations confirmed that FE65 was associated with paired helical filaments.