Brain transplants of cells expressing the carboxyl-terminal fragment of the Alzheimer amyloid protein precursor cause specific neuropathology in vivo.
Brain transplants of cells expressing the carboxyl-terminal fragment of the Alzheimer amyloid protein precursor cause specific neuropathology in vivo.
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表达阿尔茨海默淀粉样蛋白前体羧基末端片段的细胞的脑移植会在体内引起特定的神经病理学。
DOI：
10.1073/pnas.89.8.3448
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发表时间：
1992
影响因子：
11.1
通讯作者：
Hohmann,CF
中科院分区：
文献类型：
--
作者：
Neve,RL;Kammesheidt,A;Hohmann,CF
将用表达阿尔茨海默淀粉样蛋白前体（β APP-C104）的羧基末端104个氨基酸的逆转录病毒重组体转染的PC 12细胞或仅用逆转录病毒载体（DO）转染的PC 12细胞移植到新生小鼠的脑中。移植后20天，在所有检查的小鼠脑中均可检测到移植物。移植后4个月，实验动物表现出明显的皮质萎缩。一些人还发现了与Alz-50的免疫反应性，Alz-50是一种检测阿尔茨海默病相关蛋白的抗体，位于移植物周围皮层神经元的体树突结构域。此外，通过对淀粉样蛋白前体羧基末端的抗体染色，发现移植物同侧海马CA 2/3区的神经元结构紊乱。用该抗体还检测到淀粉样蛋白前体的这一部分的细胞体免疫反应性降低。总之，这些结果表明β APP的羧基末端片段可能导致体内特定的神经病理学和神经变性。
PC12 cells transfected with retroviral recombinants expressing the carboxyl-terminal 104 amino acids of the Alzheimer amyloid protein precursor (beta APP-C104) or PC12 cells transfected with the retroviral vector (DO) alone were transplanted into the brains of newborn mice. At 20 days after grafting, transplants could be detected in all of the mouse brains examined. At 4 months after transplantation, experimental animals exhibited significant cortical atrophy. Some also revealed immunoreactivity with Alz-50, an antibody that detects an Alzheimer disease-related protein, in the somatodendritic domain of neurons in the cortex surrounding the transplants. In addition, disorganization of the neuropil in the CA2/3 region of the hippocampus ipsilateral to the transplant was revealed by staining with an antibody to the carboxyl-terminal end of the amyloid protein precursor. A decrease in cell body immunoreactivity for this portion of the amyloid protein precursor was also detected with this antibody. Together, these results suggest that the carboxyl-terminal fragment of beta APP may cause specific neuropathology and neurodegeneration in vivo.