This review shows how our microbiome influences health and ultimately how well we age. Evidence linking oral bacteria to Alzheimer's disease (AD) is discussed in the context of aging, drawing together data from epidemiological, experimental, genetic and environmental studies. Immunosenescence results in increased bacterial load as cell-mediated and humoral immune responses wane, with the innate immune system contributing to a rise in circulating proinflammatory cytokines such as TNF and IL1β. Aging may favor the proliferation of anaerobes in the mouth eliciting a robust TNF response from the oral epithelium. Maintaining the integrity of the blood-brain-barrier (BBB) against a backdrop of increasing bacterial load is important; prolonged exposure to high levels of TNF compromises its integrity. Sensitive techniques now detect the “asymptomatic” presence of bacteria in areas previously thought as sterile, providing new insights into the wider distribution of components of the microbiome. These “immune-tolerated” bacteria may slowly multiply elsewhere until they elicit a chronic inflammatory response; some being considered causal in instances of atherosclerosis and back pain. Inflammatory processes, long associated with AD, have recently been further elucidated, in particular revealing the role of the inflammasomes. We propose for a subset of AD patients, aging favors the overgrowth of oral anaerobes, established earlier in life, provoking a pro-inflammatory innate response that weakens the BBB allowing bacteria to spread and quietly influence the pathogenesis of AD. Finally, we suggest that human polymorphisms, considered alongside components of the microbiome, may provide new avenues of research for the prevention and treatment of disease.
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