AmeliMojarad Melika, AmeliMojarad Mandana, Cui Xiaonan
Department of Oncology, The First Affiliate Hospital of Dalian Medical University, Zhongshan Road, Dalian, Liaoning 116011, China.
Ageing Res Rev. 2025 Feb;104:102615. doi: 10.1016/j.arr.2024.102615. Epub 2024 Dec 2.
Alzheimer's disease (AD) is the most common type of dementia which affects over than 60 million cases worldwide with higher incidence in low and middle-income countries by 2030. Based on the multifactorial nature of AD different risk factors are linked to the condition considering the brain's β-amyloid plaques (Aβ) and neurofibrillary tangles (NFTs) as its primary hallmarks. Lately, viral photogenes specially after recent SARS-CoV-2 pandemic has gained a lot of attention in promoting the neurodegenerative disorder such as AD based on their capacity to increase the permeability of the blood-brain barrier, dysregulation of immune responses, and the impact on Aβ processing and phosphorylation of tau proteins. Therefore, in this review, we summarized the important association of viral pathogens and their mechanism by which they contribute with AD formation and development. AN OVERVIEW OF THE ROLES OF VIRAL PATHOGENS IN AD: According to this figure, viruses can infect neurons directly by modulating the BBB, transferring from endothelial cells to glial cells and then to neurons, increasing the Aβ deposition, and affecting the tau protein phosphorylation or indirectly through the virus's entrance and pathogenicity that can be accelerated by genetic and epigenetic factors, as well as chronic neuroinflammation caused by activated microglia and astrocytes.
阿尔茨海默病(AD)是最常见的痴呆类型,全球有超过6000万病例受其影响,到2030年,低收入和中等收入国家的发病率将更高。基于AD的多因素性质,考虑到大脑的β-淀粉样蛋白斑块(Aβ)和神经原纤维缠结(NFTs)是其主要标志,不同的风险因素与该病相关。最近,病毒病原体,特别是在近期的严重急性呼吸综合征冠状病毒2(SARS-CoV-2)大流行之后,因其能够增加血脑屏障的通透性、免疫反应失调以及对Aβ加工和tau蛋白磷酸化的影响,在促进诸如AD等神经退行性疾病方面受到了广泛关注。因此,在本综述中,我们总结了病毒病原体的重要关联及其在AD形成和发展中的作用机制。病毒病原体在AD中的作用概述:根据此图,病毒可通过调节血脑屏障直接感染神经元,从内皮细胞转移至神经胶质细胞然后再到神经元,增加Aβ沉积,并影响tau蛋白磷酸化,或者通过病毒的进入和致病性间接起作用,而遗传和表观遗传因素以及由活化的小胶质细胞和星形胶质细胞引起的慢性神经炎症可加速病毒的进入和致病性。