Delatour B, Mercken L, El Hachimi K H, Colle M A, Pradier L, Duyckaerts C
Laboratoire de Neuropathologie Escourolle, Inserm U106, Université Paris VI, Paris. Aventis Pharma, Paris, France.
Am J Pathol. 2001 May;158(5):1585-91. doi: 10.1016/S0002-9440(10)64113-2.
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 was 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 beta-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.
FE65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FE65在阿尔茨海默病（AD）的发病机制中发挥作用。本研究旨在探究在AD病程中FE65免疫反应性的分布是否受到影响，并确定FE65与其他已知参与AD的蛋白质的共定位程度。对6例散发性AD患者和6例年龄匹配的非痴呆对照进行的单免疫过氧化物酶标记实验表明，AD患者等皮质中FE65免疫反应性所占体积比例未发生改变。然而，在海马CA4区，FE65免疫反应性增加似乎与疾病严重程度相关。双免疫荧光标记未显示FE65与淀粉样前体蛋白有任何明显的共定位。β-淀粉样肽的局灶性和弥漫性沉积物中也没有FE65免疫反应性。出乎意料的是，双重标记实验显示FE65与tau蛋白在细胞内缠结中共定位。超微结构观察证实FE65与双螺旋丝相关。
