Dumanis Sonya B, Tesoriero Joseph A, Babus Lenard W, Nguyen Madeline T, Trotter Justin H, Ladu Mary Jo, Weeber Edwin J, Turner R Scott, Xu Baoji, Rebeck G William, Hoe Hyang-Sook
Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA.
J Neurosci. 2009 Dec 2;29(48):15317-22. doi: 10.1523/JNEUROSCI.4026-09.2009.
The three human alleles of apolipoprotein E (APOE) differentially influence outcome after CNS injury and affect one's risk of developing Alzheimer's disease (AD). It remains unclear how ApoE isoforms contribute to various AD-related pathological changes (e.g., amyloid plaques and synaptic and neuron loss). Here, we systematically examined whether apoE isoforms (E2, E3, E4) exhibit differential effects on dendritic spine density and morphology in APOE targeted replacement (TR) mice, which lack AD pathological changes. Using Golgi staining, we found age-dependent effects of APOE4 on spine density in the cortex. The APOE4 TR mice had significantly reduced spine density at three independent time points (4 weeks, 3 months, and 1 year, 27.7% +/- 7.4%, 24.4% +/- 8.6%, and 55.6% +/- 10.5%, respectively) compared with APOE3 TR mice and APOE2 TR mice. Additionally, in APOE4 TR mice, shorter spines were evident compared with other APOE TR mice at 1 year. APOE2 TR mice exhibited longer spines as well as significantly increased apical dendritic arborization in the cortex compared with APOE4 and APOE3 TR mice at 4 weeks. However, there were no differences in spine density across APOE genotypes in hippocampus. These findings demonstrate that apoE isoforms differentially affect dendritic complexity and spine formation, suggesting a role for APOE genotypes not only in acute and chronic brain injuries including AD, but also in normal brain functions.
载脂蛋白E（APOE）的三种人类等位基因对中枢神经系统损伤后的预后有不同影响，并影响个体患阿尔茨海默病（AD）的风险。目前尚不清楚载脂蛋白E异构体如何导致各种与AD相关的病理变化（例如淀粉样斑块以及突触和神经元丧失）。在此，我们系统地研究了载脂蛋白E异构体（E2、E3、E4）对缺乏AD病理变化的APOE靶向替换（TR）小鼠树突棘密度和形态是否具有不同影响。使用高尔基染色法，我们发现APOE4对皮质中树突棘密度具有年龄依赖性影响。与APOE3 TR小鼠和APOE2 TR小鼠相比，APOE4 TR小鼠在三个独立时间点（4周、3个月和1年，分别为27.7%±7.4%、24.4%±8.6%和55.6%±10.5%）的树突棘密度显著降低。此外，在1岁时，与其他APOE TR小鼠相比，APOE4 TR小鼠的树突棘更短。在4周龄时，与APOE4和APOE3 TR小鼠相比，APOE2 TR小鼠的树突棘更长，并且皮质中的顶端树突分支显著增加。然而，海马体中不同APOE基因型的树突棘密度没有差异。这些发现表明，载脂蛋白E异构体对树突复杂性和树突棘形成有不同影响，这表明APOE基因型不仅在包括AD在内的急慢性脑损伤中起作用，而且在正常脑功能中也起作用。
