Puttfarcken P S, Manelli A M, Falduto M T, Getz G S, LaDu M J
Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, IL 60064-3500, USA.
J Neurochem. 1997 Feb;68(2):760-9. doi: 10.1046/j.1471-4159.1997.68020760.x.
The correlation between the epsilon 4 allele of apolipoprotein E (apoE) and Alzheimer's disease is well established. However, the role of apoE in normal as well as pathological brain processes remains unclear. We evaluated the effect of apoE treatment on development and beta-amyloid (A beta)-induced toxicity using primary cultures of developing rat hippocampal neurons. The source of apoE was conditioned media from HEK cells stably transfected with human apoE3 or apoE4 cDNA, a preparation where apoE is lipid-associated. Morphological and biochemical changes in the cultures were assessed at 1 and 3 days following low- and high-density plating with either apoE3 or E4 with or without A beta. Both apoE isoforms were neurotrophic, as measured by increased neurite length. Aged A beta(1-42), a peptide preparation exhibiting extensive fibril and aggregate formation, is toxic to these cultures. Addition of apoE3 and E4 significantly and comparably attenuated the A beta-induced reduction in both neurite length and cell viability. The level of protection against this toxicity was proportional to the neurotrophic actions of the two apoE isoforms. Thus, apoE acts as a potent growth factor in both the absence and the presence of A beta, supporting a potentially important role for apoE in neurobiology.
载脂蛋白E（apoE）的ε4等位基因与阿尔茨海默病之间的相关性已得到充分证实。然而，apoE在正常以及病理脑过程中的作用仍不清楚。我们使用发育中的大鼠海马神经元原代培养物评估了apoE处理对发育和β-淀粉样蛋白（Aβ）诱导毒性的影响。apoE的来源是用人类apoE3或apoE4 cDNA稳定转染的HEK细胞的条件培养基，这是一种apoE与脂质相关的制剂。在用apoE3或E4进行低密度和高密度接种后，在第1天和第3天评估培养物中的形态学和生化变化，接种时添加或不添加Aβ。通过增加的神经突长度测量，两种apoE亚型均具有神经营养作用。老化的Aβ（1-42），一种表现出广泛纤维和聚集体形成的肽制剂，对这些培养物有毒性。添加apoE3和E4显著且相当程度地减轻了Aβ诱导的神经突长度和细胞活力的降低。针对这种毒性的保护水平与两种apoE亚型的神经营养作用成正比。因此，无论有无Aβ，apoE都作为一种有效的生长因子发挥作用，支持apoE在神经生物学中具有潜在的重要作用。
