The role of microbial infection in the pathogenesis of Alzheimer’s disease and the opportunity for protection by anti-microbial peptides

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.