QPS Austria, Grambach, Austria; Institute of Molecular Biology and Biochemistry, Medical University Graz, Graz, Austria.
Neurobiol Aging. 2013 Oct;34(10):2379-88. doi: 10.1016/j.neurobiolaging.2013.04.008. Epub 2013 May 3.
During their lifetime, people are commonly exposed to several vascular risk factors that may affect brain ageing and cognitive function. In the last few years, increasing evidence suggests that pathological plasma lipid profiles contribute to the pathogenesis of late-onset Alzheimer's disease. Importantly, hypercholesterolemia, especially elevated low-density lipoprotein cholesterol values, that is, increased apolipoprotein B-100 (ApoB-100) levels, represents an independent risk factor. In this study, the effects of ApoB-100 overexpression, either alone or in combination with cerebral expression of human amyloid precursor protein (hAPP), on cognitive functions and brain pathology were assessed. Our results show that ApoB-100 overexpression induces memory decline and increases cerebral lipid peroxidation and amyloid beta levels compared to those in wild-type animals. Although double-transgenic ApoBxAPP animals did not develop more distinct behavioral deficits than single-transgenic hAPP littermates, hApoB-100 expression caused additional pathophysiological features, such as high LDL and low HDL-cholesterol levels, increased lipid peroxidation, and pronounced ApoB-100 accumulation in cerebral vessels. Thus, our results indicate that ApoBxAPP mice might better reflect the situation of elderly humans than hAPPsl overexpression alone.
在人的一生当中，通常会接触到多种可能影响大脑衰老和认知功能的血管危险因素。近年来，越来越多的证据表明，病理性的血浆脂质谱有助于晚期阿尔茨海默病的发病机制。重要的是，高胆固醇血症，特别是低密度脂蛋白胆固醇值升高，即载脂蛋白 B-100（ApoB-100）水平增加，是一个独立的危险因素。在这项研究中，评估了单独过表达 ApoB-100 或与人类淀粉样前体蛋白（hAPP）在大脑中的表达相结合，对认知功能和脑病理学的影响。我们的结果表明，与野生型动物相比，ApoB-100 的过表达会导致记忆下降，并增加大脑脂质过氧化和淀粉样β水平。尽管 ApoBxAPP 双转基因动物比 hAPP 单转基因同窝仔动物没有表现出更明显的行为缺陷，但 hApoB-100 的表达会导致其他病理生理特征，如 LDL 升高和 HDL-胆固醇水平降低、脂质过氧化增加以及 ApoB-100 在大脑血管中的大量蓄积。因此，我们的研究结果表明，ApoBxAPP 小鼠可能比单独过表达 hAPPsl 更能反映老年人群的情况。
