The ɛ4 allele of the Apolipoprotein E (APOE) gene in individuals infected by Herpes simplex virus type 1 (HSV-1) has been demonstrated to be a risk factor in Alzheimer’s disease (AD). APOE-ɛ4 reduces the levels of neuronal cholesterol, interferes with the transportation of cholesterol, impairs repair of synapses, decreases the clearance of neurotoxic peptide amyloid-β (Aβ), and promotes the deposition of amyloid plaque, and eventually may cause development of AD. HSV-1 enters host cells and can infect the olfactory system, trigeminal ganglia, entorhinal cortex, and hippocampus, and may cause AD-like pathological changes. The lifecycle of HSV-1 goes through a long latent phase. HSV-1 induces neurotropic cytokine expression with pro-inflammatory action and inhibits antiviral cytokine production in AD. It should be noted that interferons display antiviral activity in HSV-1-infected AD patients. Reactivated HSV-1 is associated with infectious burden in cognitive decline and AD. Finally, HSV-1 DNA has been confirmed as present in human brains and is associated with APOE ɛ4 in AD. HSV-1 and APOE ɛ4 increase the risk of AD and relate to abnormal autophagy, higher concentrations of HSV-1 DNA in AD, and formation of Aβ plaques and neurofibrillary tangles.

中文翻译：

---

载脂蛋白Eɛ4基因型和单纯疱疹病毒1型在阿尔茨海默病中的独立和相关作用

载脂蛋白E（APOE）基因的ɛ4等位基因在被单纯疱疹病毒1型（HSV-1）感染的个体中已被证明是阿尔茨海默氏病（AD）的危险因素。APOE-ɛ4降低神经元胆固醇的水平，干扰胆固醇的运输，削弱突触的修复，降低神经毒性肽淀粉样蛋白-β（Aβ）的清除，并促进淀粉样斑块的沉积，最终可能导致AD的发展。HSV-1进入宿主细胞，可感染嗅觉系统，三叉神经节，内嗅皮质和海马，并可能引起AD样病理改变。HSV-1的生命周期经历了很长的潜在阶段。HSV-1诱导具有促炎作用的嗜神经细胞因子表达，并抑制AD中抗病毒细胞因子的产生。应当指出，干扰素在感染HSV-1的AD患者中显示抗病毒活性。再次激活的HSV-1与认知能力下降和AD的感染负担相关。最后，已经证实HSV-1 DNA存在于人脑中，并且与AD中的APOEɛ4有关。HSV-1和APOEɛ4会增加AD的风险，并与异常的自噬，AD中HSV-1 DNA的浓度较高以及Aβ斑块和神经原纤维缠结的形成有关。