Division of Brain Diseases, Center for Biomedical Sciences, Korea National Institute of Health, 187 Osongsaengmyeong2-ro, Osong-eup, Heungdeok-gu, Cheongju-si, Chungcheongbuk-do, 28159, Korea.
Departments of Neurology, Korea University Medical College, Ansan Hospital, 123 Jeokgeum-ro, Danwon-gu, Ansan-si, Gyeonggi-do, 15355, Korea.
Sci Rep. 2017 Dec 18;7(1):17713. doi: 10.1038/s41598-017-18042-1.
Alzheimer's disease (AD) is a common disorder of progressive cognitive decline among elderly subjects. Angiogenesis-related factors including vascular endothelial growth factor (VEGF) might be involved in the pathogenesis of AD. Soluble form of the VEGF receptor is likely to be an intrinsic negative counterpart of VEGF. We measured the plasma levels of VEGF and its two soluble receptors (sVEGFR1 and sVEGFR2) in 120 control subjects, 75 patients with mild cognitive impairment, and 76 patients with AD using ELISA. Plasma levels of VEGF in patients with AD were higher than those in healthy control subjects. However, plasma levels of sVEGFR1 and sVEGFR2 were lower in patients with AD than in healthy control subjects. Levels of VEGFR2 mRNA were significantly decreased in human umbilical vein endothelial cells after amyloid-beta treatment. Further, protein levels of VEGFR2 were also decreased in the brains of AD model mice. In addition, we show that the expression of sVEGFR2 and VEGFR2 was also decreased by the transfection with the Notch intracellular domain. These results indicate that the alterations of VEGF and its two receptors levels might be associated with those at risk for Alzheimer's disease.
阿尔茨海默病（AD）是老年人进行性认知功能下降的常见疾病。血管生成相关因素，包括血管内皮生长因子（VEGF），可能参与 AD 的发病机制。VEGF 的可溶性受体可能是 VEGF 的内在负性对应物。我们使用 ELISA 法测量了 120 名对照受试者、75 名轻度认知障碍患者和 76 名 AD 患者的 VEGF 及其两种可溶性受体（sVEGFR1 和 sVEGFR2）的血浆水平。AD 患者的 VEGF 血浆水平高于健康对照组。然而，AD 患者的 sVEGFR1 和 sVEGFR2 血浆水平低于健康对照组。淀粉样β处理后人脐静脉内皮细胞中 VEGFR2 mRNA 水平显著降低。此外，AD 模型小鼠大脑中 VEGFR2 蛋白水平也降低。此外，我们还表明，Notch 细胞内结构域的转染也降低了 sVEGFR2 和 VEGFR2 的表达。这些结果表明，VEGF 及其两种受体水平的改变可能与阿尔茨海默病的风险相关。
