Lovestone S, Anderton B H, Hartley C, Jensen T G, Jorgensen A L
Section of Old Age Psychiatry, Institute of Psychiatry, London, UK.
Neuroreport. 1996 Apr 10;7(5):1005-8. doi: 10.1097/00001756-199604100-00010.
The apolipoprotein E (apoE) gene has been identified as a susceptibility gene for Alzheimer's disease, although the mechanism whereby apoE exerts this effect has not been determined. The aim of this study was to examine the intracellular fate of apoE and we demonstrate that in mammalian cells-transiently expressing tau and the low density lipoprotein receptor, apoE is taken up from cerebrospinal fluid (CSF) and apoE3, but not apoE4, reaches the cytoplasm. This isoform difference in the intracellular distribution of apoE is dependent upon tau expression and, although tau phosphorylation was not affected by apoE, these results suggest that apoE interactions with the cytoskeleton might be important in the molecular pathogenesis of Alzheimer's disease.
载脂蛋白E(apoE)基因已被确定为阿尔茨海默病的一个易感基因,尽管apoE发挥这种作用的机制尚未确定。本研究的目的是检测apoE在细胞内的命运,我们证明,在瞬时表达tau蛋白和低密度脂蛋白受体的哺乳动物细胞中,apoE能从脑脊液(CSF)中摄取,且载脂蛋白E3(apoE3)而非载脂蛋白E4(apoE4)能进入细胞质。apoE在细胞内分布的这种异构体差异取决于tau蛋白的表达,并且,尽管tau蛋白的磷酸化不受apoE的影响,但这些结果表明,apoE与细胞骨架的相互作用可能在阿尔茨海默病的分子发病机制中起重要作用。