Alzheimer病（AD）是引起痴呆最常见原因,目前尚无有效治疗。现在AD被认为是一系列病理事件共同平行参与下的结果。神经干细胞（NSCs）在体外培养过程中可以分泌微泡及各种神经营养因子进入到条件培养基（CM）中， 且NSC-CM可以自由通过血脑屏障。研究证实NSC-CM具有抗凋亡、促进内源性NSCs的增殖和神经元分化和迁移、抑制颅内炎症反应及促进新生血管生成作用。本项目采用Aβ25-35预处理的SH-SY5Y细胞作为AD 的细胞模型，APP/PS1转基因小鼠作为AD动物模型，分别给予NSC-CM干预，观察其对AD 细胞模型凋亡影响；观察其对APP/PS1小鼠认知功能的影响、脑内神经干细胞增殖和神经元分化凋亡、炎症反应、及血管再生的变化。评估NSC-CM干预AD细胞和动物模型可能的机制。以期为AD的治疗提供新的治疗方法的理论依据。

Alzheimer’s disease (AD) is the most common cause of dementia. There are no drugs to cure AD. AD is considered to be the pathological network with several pathological events running in parallel. Thus, the most realistic way to alter the natural course of AD should involve the simultaneous modulation of several key biological targets. It has been well accepted that neural stem cells (NSCs) can target several key pathological events to exert neuroprotection by paracrine effects, not cell replacement. However, safety concerns，which include rejection of transplants, the risk of tuorigenicity, the difficulty of transplantation route, the ethical limitation, limit its clinical application. NSCs can secret microvesicles (MVs) and different kinds of nerve growth factors into conditioned medium (CM), which can penetrate blood brain barrier. It has been confirmed that NSC-CM in vivo own these capacities, which include anti-apoptosis, enhancing the proliferation, and neuron differentiation of endoneurogenesis, enhancing the genesis of new vessels, and inhibiting the inflammatory process. Thus, we use Aβ25-35 pretreated SH-SY5Y cells as cell model of AD to testify the protective against apoptosis of NSC-CM. Further, we apply aged 5 months male APP/PS1 transgenic mice as the animal model of AD to observe the neuroprotective effect of NSC-CM and analyze the possible mechanisms.