Neuroscience Department, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain.
Laboratory of personalized medicine, Epigenomics Unit, Medical Research Institute La Fe, Valencia, Spain.
Sci Rep. 2018 Apr 24;8(1):6434. doi: 10.1038/s41598-018-24710-7.
The risk of suffering from Alzheimer's disease (AD) is higher in individuals from AD-affected mothers. The purpose of this investigation was to study whether maternal transmission might produce AD-related alterations in progenies of mice that do not have any genotypic alteration. We used cognitively-intact mothers harbouring in heterozygosity the transgene for overexpressing the Swedish double mutant version of the human amyloid precursor protein (hAβPPswe). The phenotype of the offspring with or without the transgene resulting from crossing young Tg2576 females with wild-type males were compared with those of the offspring resulting from crossing wild-type females with Tg2576 males. The hAβPPswe-bearing offspring from Tg2576 mothers showed an aggravated AD-like phenotype. Remarkably, cognitive, immunohistochemical and some biochemical features displayed by Tg2576 heterozygous mice were also found in wild-type animals generated from Tg2576 females. This suggests the existence of a maternal imprinting in the wild-type offspring that confers a greater facility to launch an AD-like neurodegenerative cascade. Such progeny, lacking any mutant amyloid precursor protein, constitutes a novel model to study maternal transmission of AD and, even more important, to discover early risk markers that predispose to the development of AD.
患阿尔茨海默病（AD）的风险在受 AD 影响的母亲的子女中更高。本研究的目的是研究母体传递是否会导致没有任何基因型改变的小鼠后代产生与 AD 相关的改变。我们使用认知功能正常的携带有过表达人淀粉样前体蛋白（hAβPPswe）瑞典双突变体转基因的杂合子母亲。来自携带转基因的年轻 Tg2576 雌性与野生型雄性杂交的后代与来自携带野生型雌性与 Tg2576 雄性杂交的后代的表型进行了比较。来自 Tg2576 母亲的携带 hAβPPswe 的后代表现出加重的 AD 样表型。值得注意的是，Tg2576 杂合子小鼠表现出的认知、免疫组织化学和一些生化特征也存在于来自 Tg2576 雌性的野生型动物中。这表明在野生型后代中存在母体印迹，赋予了启动 AD 样神经退行性级联更大的能力。这种缺乏任何突变淀粉样前体蛋白的后代构成了研究 AD 的母体传递的新模型，甚至更重要的是，发现了易患 AD 发展的早期风险标志物。
