Yadav Pardeep, Lee Yeon-Hee, Panday Hrithika, Kant Shubham, Bajwa Neha, Parashar Ritika, Jha Saurabh Kumar, Jha Niraj Kumar, Nand Parma, Lee Sang-Soo, Jha Abhimanyu Kumar
Department of Biotechnology, School of Engineering & Technology, Sharda University, Greater Noida 201310, Uttar Pradesh, India.
Institute for Skeletal Aging & Orthopedic Surgery, Hallym University-Chuncheon Sacred Heart Hospital, Chuncheon-si 24252, Gangwon-do, Korea.
Curr Issues Mol Biol. 2022 Sep 30;44(10):4584-4615. doi: 10.3390/cimb44100314.
Alzheimer's disease (AD) is a deadly brain degenerative disorder that leads to brain shrinkage and dementia. AD is manifested with hyperphosphorylated tau protein levels and amyloid beta (Aβ) peptide buildup in the hippocampus and cortex regions of the brain. The nervous tissue of AD patients also contains fungal proteins and DNA which are linked to bacterial infections, suggesting that polymicrobial infections also occur in the brains of those with AD. Both immunohistochemistry and next-generation sequencing (NGS) techniques were employed to assess fungal and bacterial infections in the brain tissue of AD patients and non-AD controls, with the most prevalent fungus genera detected in AD patients being Alternaria, Botrytis, Candida, and Malassezia. Interestingly, Fusarium was the most common genus detected in the control group. Both AD patients and controls were also detectable for Proteobacteria, followed by Firmicutes, Actinobacteria, and Bacteroides for bacterial infection. At the family level, and exhibited higher levels in the brains of those with AD than the brains of the control group. Accordingly, there is thought to be a viscous cycle of uncontrolled neuroinflammation and neurodegeneration in the brain, caused by agents such as the herpes simplex virus type 1 (HSV1), , and Spirochetes, and the presence of apolipoprotein E4 (APOE4), which is associated with an increased proinflammatory response in the immune system. Systemic proinflammatory cytokines are produced by microorganisms such as Cytomegalovirus, , and those related to periodontal infections. These can then cross the blood-brain barrier (BBB) and lead to the onset of dementia. Here, we reviewed the relationship between the etiology of AD and microorganisms (such as bacterial pathogens, Herpesviridae viruses, and periodontal pathogens) according to the evidence available to understand the pathogenesis of AD. These findings might guide a targeted anti-inflammatory therapeutic approach to AD.
阿尔茨海默病（AD）是一种致命的脑部退行性疾病，会导致脑萎缩和痴呆。AD表现为大脑海马体和皮质区域中tau蛋白过度磷酸化以及β淀粉样蛋白（Aβ）肽积累。AD患者的神经组织中还含有与细菌感染相关的真菌蛋白和DNA，这表明AD患者大脑中也存在多种微生物感染。采用免疫组织化学和下一代测序（NGS）技术评估AD患者和非AD对照的脑组织中的真菌和细菌感染，在AD患者中检测到的最常见真菌属为链格孢属、葡萄孢属、念珠菌属和马拉色菌属。有趣的是，镰刀菌属是对照组中检测到的最常见属。AD患者和对照组中也都能检测到变形菌门，其次是厚壁菌门、放线菌门和拟杆菌门的细菌感染。在科水平上，[此处原文缺失相关信息]在AD患者大脑中的水平高于对照组大脑。因此，人们认为大脑中存在由单纯疱疹病毒1型（HSV1）、[此处原文缺失相关信息]和螺旋体等病原体以及与免疫系统促炎反应增加相关的载脂蛋白E4（APOE4）导致的不受控制的神经炎症和神经退行性变的恶性循环。全身性促炎细胞因子由巨细胞病毒、[此处原文缺失相关信息]和与牙周感染相关的微生物产生。这些细胞因子随后可穿过血脑屏障（BBB）并导致痴呆的发作。在此，我们根据现有证据综述了AD病因与微生物（如细菌病原体、疱疹病毒科病毒和牙周病原体）之间的关系，以了解AD的发病机制。这些发现可能会为AD的靶向抗炎治疗方法提供指导。
