Holtzman D M, Pitas R E, Kilbridge J, Nathan B, Mahley R W, Bu G, Schwartz A L
Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Proc Natl Acad Sci U S A. 1995 Oct 10;92(21):9480-4. doi: 10.1073/pnas.92.21.9480.
The epsilon 4 allele of apolipoprotein E (apoE) is a major risk factor for Alzheimer disease, suggesting that apoE may directly influence neurons in the aging brain. Recent data suggest that apoE-containing lipoproteins can influence neurite outgrowth in an isoform-specific fashion. The neuronal mediators of apoE effects have not been clarified. We show here that in a central nervous system-derived neuronal cell line, apoE3 but not apoE4 increases neurite extension. The effect of apoE3 was blocked at low nanomolar concentrations by purified 39-kDa protein that regulates ligand binding to the low density lipoprotein receptor-related protein (LRP). Anti-LRP antibody also completely abolished the neurite-promoting effect of apoE3. Understanding isoform-specific cell biological processes mediated by apoE-LRP interactions in central nervous system neurons may provide insight into Alzheimer disease pathogenesis.
载脂蛋白E（apoE）的ε4等位基因是阿尔茨海默病的主要危险因素，这表明apoE可能直接影响衰老大脑中的神经元。最近的数据表明，含apoE的脂蛋白可以以异构体特异性的方式影响神经突生长。apoE作用的神经元介质尚未阐明。我们在此表明，在一种中枢神经系统来源的神经元细胞系中，apoE3而非apoE4可增加神经突延伸。apoE3的作用在低纳摩尔浓度下被纯化的39 kDa蛋白阻断，该蛋白调节配体与低密度脂蛋白受体相关蛋白（LRP）的结合。抗LRP抗体也完全消除了apoE3的神经突促进作用。了解中枢神经系统神经元中由apoE-LRP相互作用介导的异构体特异性细胞生物学过程，可能有助于深入了解阿尔茨海默病的发病机制。
