The mechanisms of disease processes resulting in dementia of which, Alzheimer's disease (AD) is a common example, remain elusive. To this end, a number of theories as plausible explanations have been suggested. Of these, the microbial, peripheral infection theory of Hunter and Miller (1900s) and Naguchi and Moore (1913) is the earliest proposal to explain possible causation of AD. Periodontal disease is a polymicrobial inflammatory disease reported to associate with AD via periodontal bacteria/bacteraemia, systemic inflammation, blood-brain barrier erosion, intra-cerebral inflammation and tissue injury, this chapter describes the original finding of four out of 10 confirmed AD brains with incidental infection of Porphyromonas gingivalis [P. gingivalis] outer membrane component lipopolysaccharide. A follow-on study examined the possibility of P. gingivalis translocation from the gingivae to the brain in the orally infected (n=12), apoliporprotein E knockout (ApoE−/−) mouse model at 12 and 24 weeks of monoinfections. Sensitive bacterial molecular speciation techniques confirmed the invasion of P. gingivalis into the brain at 12 weeks (p=0.006), and at 24 weeks of infection (p=0.0001). Immunolabeling using antibodies against complement proteins demonstrated the innate immune system activation via C3 fragmentation and its subsequent opsonisation onto vulnerable pyramidal neurons (p=0.032) in the hippocampus as ongoing bystander injury. These studies confirm the initiation of an infection mediated inflammasome assembly with implications for remote body organ inflammatory pathologies from periodontitis to dementia.
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