Department of Nursing, College of Nursing, Gachon University, Incheon 21936, Korea.
Neuroscience Research Institute, Gachon University, Incheon 21565, Korea.
Int J Mol Sci. 2020 Apr 10;21(7):2658. doi: 10.3390/ijms21072658.
Alzheimer's disease (AD), a progressive neurodegenerative disorder, is characterized clinically by cognitive decline and pathologically by the development of amyloid plaques. AD is the most common cause of dementia among older people. However, there is currently no cure for AD. In this study, we aimed to elucidate the therapeutic effects of human amniotic epithelial stem cells (hAESCs) in a transgenic mouse model of AD. Tg2576 transgenic (Tg) mice underwent behavioral tests, namely the Morris water maze and Y-maze tests, to assess their cognitive function. In the Morris water maze test, hAESC-treated Tg mice exhibited significantly shorter escape latencies than vehicle-treated Tg mice. In the Y-maze test, hAESC-treated Tg mice exhibited significantly higher rate of spontaneous alteration than vehicle-treated Tg mice, while the total number of arm entries did not differ between the groups. Furthermore, Congo red staining revealed that hAESCs injection reduced the number of amyloid plaques present in the brains of Tg mice. Finally, beta-secretase (BACE) activity was significantly decreased in Tg mice at 60 min after hAESCs injection. In this study, we found that intracerebral injection of hAESCs alleviated cognitive impairment in a Tg2576 mouse model of AD. Our results indicate that hAESCs injection reduced amyloid plaques caused by reduced BACE activity. These results indicate that hAESCs may be a useful therapeutic agent for the treatment of AD-related memory impairment.
阿尔茨海默病（AD）是一种进行性神经退行性疾病，临床上表现为认知能力下降，病理学上表现为淀粉样斑块的形成。AD 是老年人中最常见的痴呆症病因。然而，目前尚无治疗 AD 的方法。在本研究中，我们旨在阐明人羊膜上皮干细胞（hAESCs）在 AD 转基因小鼠模型中的治疗效果。Tg2576 转基因（Tg）小鼠接受行为测试，即 Morris 水迷宫和 Y 迷宫测试，以评估其认知功能。在 Morris 水迷宫测试中，hAESC 处理的 Tg 小鼠的逃避潜伏期明显短于载体处理的 Tg 小鼠。在 Y 迷宫测试中，hAESC 处理的 Tg 小鼠的自发变化率明显高于载体处理的 Tg 小鼠，而两组的臂进入总数没有差异。此外，刚果红染色显示 hAESCs 注射减少了 Tg 小鼠大脑中存在的淀粉样斑块数量。最后，在 hAESCs 注射后 60 分钟，Tg 小鼠中的β-分泌酶（BACE）活性显著降低。在本研究中，我们发现脑内注射 hAESCs 减轻了 AD 转基因小鼠模型的认知障碍。我们的结果表明，hAESCs 注射减少了由 BACE 活性降低引起的淀粉样斑块。这些结果表明 hAESCs 可能是治疗 AD 相关记忆障碍的有效治疗剂。
