Arendt T, Schindler C, Brückner M K, Eschrich K, Bigl V, Zedlick D, Marcova L
Department of Neurochemistry, Paul Flechsig Institute of Brain Research, Leipzig, Germany.
J Neurosci. 1997 Jan 15;17(2):516-29. doi: 10.1523/JNEUROSCI.17-02-00516.1997.
A relationship between the apolipoprotein E (apoE) genotype and the risk to develop Alzheimer's disease has been established recently. Apolipoprotein synthesis is implicated in developmental processes and in neuronal repair of the adult nervous system. In the present study, we investigated the influence of the apolipoprotein polymorphism on the severity of neuronal degeneration and the extent of plastic dendritic remodeling in Alzheimer's disease. Changes in length and arborization of dendrites of Golgi-impregnated neurons in the basal nucleus of Meynert, locus coeruleus, raphe magnus nucleus, medial amygdaloid nucleus, pedunculopontine tegmental nucleus, and substantia nigra were analyzed after three-dimensional reconstruction. Patients with either one or two apoE epsilon 4 alleles not only showed a more severe degeneration in all areas investigated than in patients lacking the apoE 4 allele but also revealed significantly less plastic dendritic changes. ApoE epsilon 4 allele copy number, furthermore, had a significant effect on the pattern of dendritic arborization. Moreover, the relationship between the intensity of dendritic growth and both the extent of neuronal degeneration and the stage of the disease seen in patients lacking the apoE epsilon 4 allele was very weak in the presence of one epsilon 4 allele and completely lost in patients homozygous for the epsilon 4 allele. The results provide direct evidence that neuronal reorganization is affected severely in patients with Alzheimer's disease carrying the apoE epsilon 4 allele. This impairment of neuronal repair might lead to a more rapid functional decompensation, thereby contributing to an earlier onset and more rapid progression of the disease.
载脂蛋白E（apoE）基因型与患阿尔茨海默病风险之间的关系最近已被确立。载脂蛋白的合成与发育过程以及成年神经系统的神经元修复有关。在本研究中，我们调查了载脂蛋白多态性对阿尔茨海默病中神经元变性严重程度和树突可塑性重塑程度的影响。在进行三维重建后，分析了Meynert基底核、蓝斑、中缝大核、杏仁内侧核、脚桥被盖核和黑质中经高尔基染色的神经元树突长度和分支的变化。携带一个或两个apoEε4等位基因的患者不仅在所有研究区域中显示出比缺乏apoE 4等位基因的患者更严重的变性，而且还显示出明显更少的树突可塑性变化。此外，apoEε4等位基因拷贝数对树突分支模式有显著影响。此外，在缺乏apoEε4等位基因的患者中所见的树突生长强度与神经元变性程度和疾病阶段之间的关系，在存在一个ε4等位基因时非常微弱，而在ε4等位基因纯合的患者中则完全消失。这些结果提供了直接证据，表明携带apoEε4等位基因的阿尔茨海默病患者的神经元重组受到严重影响。这种神经元修复的损害可能导致更快的功能失代偿，从而导致疾病更早发作和进展更快。
