Abstract

Alzheimer’s disease (AD) is the most common cause of dementia. Its pathology is primarily characterized by extracellular deposits of amyloid β peptide and intracellular neurofibrillary tangles. Current rationales to explain the pathogenesis of AD include amyloid cascade, inflammation, infection defense and anti-microbial protection hypotheses. This review focuses on recent advances in the infection hypothesis, in particular on those pathogenic microbes that act systemically, via periodontal and gastro-intestinal infection routes. It is proposed that the evidence convincingly supports that pathogenic microbial infection is associated with, and is likely a causative trigger for, AD pathology. Microbes can drive AD pathology by two main pathways: either by directly infecting the brain and stimulating amyloid-mediated defence (causative trigger) or indirectly, by stimulating the pro-inflammatory effects of infection. In this context, it follows that anti-microbial/anti-infection therapies could be effective for regulating the pathology and symptoms of AD, depending on the stage of disease. As long-term administration of traditional antibiotic therapy is not recommended, alternative antibiotic agents such as anti-microbial peptides (AMPs), could be preferred for intervention and disease management of AD.

摘要

阿尔茨海默氏病（AD）是痴呆症的最常见原因。其病理学的主要特征是淀粉样β肽的细胞外沉积和细胞内神经原纤维缠结。当前解释AD发病机理的基本原理包括淀粉样蛋白级联反应，炎症，感染防御和抗微生物保护假说。这项审查集中在感染假说的最新进展，特别是那些通过牙周和胃肠道感染途径系统性起作用的病原微生物。有人提出有说服力的证据支持病原微生物感染与AD病理相关，并且可能是AD病理的诱因。微生物可以通过两种主要途径推动AD病理：通过直接感染大脑并刺激淀粉样蛋白介导的防御作用（病因触发），或通过刺激感染的促炎作用间接地进行。在这种情况下，可以得出结论，取决于疾病的阶段，抗微生物/抗感染疗法可能有效地调节了AD的病理和症状。由于不建议长期使用传统抗生素治疗，因此替代性抗生素药物（例如抗微生物肽（AMPs））可能是AD的干预和疾病管理的首选方法。