The role of microbial infection in the pathogenesis of Alzheimer’s disease and the opportunity for protection by anti-microbial peptides
Feijie Li, Milton T. W. Hearn, Louise E. Bennett
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.