老年痴呆是一种最为常见的神经退行性疾病，是痴呆症的首要病因。老年痴呆的两大病理特征表现为大脑神经细胞外主要由β淀粉样蛋白（Aβ）组成的淀粉样斑，和细胞内由高度磷酸化的微管相关蛋白（Tau）组成的神经纤维缠结。载脂蛋白E（APOE）基因的ε4等位基因是导致老年痴呆的最重要的风险因子，而其单独存在并不足以引起老年痴呆。人群中I型单纯疱疹病毒（HSV-1）的感染率高达50%-90%。HSV-1具有嗜神经性，携带APOE ε4等位基因协同HSV-1感染中枢神经系统可能导致老年痴呆，而其协同作用的分子机制还不清楚。本课题拟通过实时荧光定量PCR、酶联免疫吸附试验、免疫印迹、流式细胞术等细胞和分子生物学实验方法，研究不同亚型ApoE影响HSV-1感染并损伤神经细胞的分子机制，深入阐明ApoE4协同HSV-1感染导致老年痴呆高风险的分子机制，为预防和治疗老年痴呆提供新思路以及理论依据。

Alzheimer's disease (AD) is the most common neurodegenerative disease, and it is a major cause of dementia. AD patients have two hallmarks in the brain: the extracellular amyloid plaques primarily composed of amyloid β (Aβ), and the intracellular neurofibrillary tangles comprised of hyperphosphorylated microtubule-associated protein Tau. The ε4 allele of Apolipoprotein E (APOE) gene is a major risk factor for AD, but its own is not enough to lead to AD. The infection of herpes simplex virus type 1 (HSV-1) among the population are as high as 50% to 90%. HSV-1 is neurotropic, and the presence of APOE ε4 allele and HSV-1 infection in the brain might synergistically cause AD, however, it is unclear how they synergistically function in the pathogenesis of AD. This project intends to make use of a series of cellular and molecular biology methods, including Real-time PCR, ELISA, Western Blot, Flow cytometry, to study the effects of different ApoE isoforms on HSV-1 infection and injury to neuronal cells, and to better elucidate the molecular mechanisms of ApoE4 and HSV-1 infection as synergistic risk factors for AD. This might allow us to identify novel strategies for AD prevention and therapy.