APP/PS1双转基因阿尔茨海默氏病鼠的神经发生与Prion蛋白的关系

Alzheimer's disease (AD), the most common adult onset dementia。 Cellular prion protein ,a high affinity receptor for Aβ oligomers（basic pathology of AD）is one of main protein related to cognition function.Prion expression is increasing in AD patient's brain, at the same time,neurogenesis is increasing in AD patient's hippocampus.Are prion protein and neurogenesis related ? Acturally, prion participates to embryo and adult neurogenesis. Prion protein is important for neural precursors differentiation to neuron.Is prion protein important to neurogenesis or regulate neurogenesis in AD? Our former research found:1)Prion protein gene ( Prnp) codon 129 polymorphism was relevant to AD;2)Neurogenesis increased in the progressive stage of APP/PS1 double transgenic mice;3)APP/PS1 double transgenic mice cognitive function declined . Based on this idea,we design this experiment using APP/PS1 double transgenic mice through in vivo and in vitro experiments. The study will focus on prion protein and neurogenesis in AD through neural stem cell culture,cell differentiation,siRNA transfection,behavior test,immunohistochemistry.

阿尔茨海默氏病是老年期最常见的痴呆类型。研究发现Prion蛋白是可溶性Aβ低聚物（AD主要病理基础）的高亲和力受体。这表明Prion蛋白是一种与认知功能相关的重要蛋白。Prion蛋白在AD病人的脑中表达是增加的，而AD病人脑海马新生细胞数也是增加的。那么Prion蛋白与神经发生是否有关？事实上，Prion蛋白参与整个胚胎的神经发生，及成年哺乳动物的神经发生，主要参与神经前体细胞向成熟神经元的分化。那么Prion蛋白是否参与AD的神经发生或调控？我们前期实验发现：1.Prion蛋白基因129密码子多态性与AD相关；2.APP/PS1双转基因鼠的神经发生是增加的;3.随年龄增大APP/PS1双转基因鼠认知功能逐渐下降。基于以上观点，采用APP/PS1双转基因AD鼠模型，体内及体外试验，转基因鼠神经干细胞培养、分化、siRNA转染，行为学试验，免疫组织化学研究Prion蛋白与AD神经发生的关系。