Provias John, Jeynes Brian
Department of Pathology and Molecular Medicine [Neuropathology], Hamilton Health Sciences, McMaster University, Hamilton, ON, Canada L8L 2X2.
Patholog Res Int. 2010;2010:173496. doi: 10.4061/2010/173496.
This study is one of the few to characterize immunohistochemically the distribution and localization of Receptor-Associated Protein (RAP) in human autopsy brain. The results show prominent cortical neuronal localization. RAP is clearly identified in large neuronal dendritic/axonal processes. RAP is expressed in both large pyramidal and smaller interneurons. Occasional, much less frequent RAP is detectable in glial cells in white matter, which appear to be predominantly astrocytic. Although RAP is detectable immunohistochemically in Alzheimer's disease autopsy brain, the level of expression appears significantly reduced relative to age-matched control brains. These results suggest, at the immunohistochemical level, that there is a reduction of RAP protein in Alzheimer's disease brain (cortex). In terms of Alzheimer's disease pathophysiology, a reduction of neuronal RAP could then lead to reduced membrane expression of LRP, since RAP has also been shown to be an LRP antagonist.
本研究是少数通过免疫组织化学方法对人尸检脑内受体相关蛋白（RAP）的分布和定位进行表征的研究之一。结果显示其在皮质神经元中定位显著。在大的神经元树突/轴突过程中可清晰鉴定出RAP。RAP在大型锥体细胞和较小的中间神经元中均有表达。在白质的胶质细胞中偶尔能检测到RAP，但频率要低得多，这些胶质细胞似乎主要是星形胶质细胞。虽然在阿尔茨海默病尸检脑中通过免疫组织化学可检测到RAP，但其表达水平相对于年龄匹配的对照脑明显降低。这些结果在免疫组织化学水平上表明，阿尔茨海默病脑（皮质）中RAP蛋白减少。就阿尔茨海默病的病理生理学而言，神经元RAP的减少可能会导致低密度脂蛋白受体相关蛋白（LRP）的膜表达降低，因为RAP也已被证明是一种LRP拮抗剂。
