Abstract
ABSTRACTChronic periodontitis of 10 years’ duration is reported to become a twofold risk factor for the development of Alzheimer’s disease (AD). Periodontitis is modifiable, and this fits with the current action plan for preventing AD. However, until periodontitis, becomes acknowledged as a firm risk factor for AD, this risk will continue. Here, we put forward our own argument based on the current literature for in vivo infection-mediated periodontal disease models supporting the antimicrobial protection hypothesis of AD and interventional studies supporting the causal links. Oral infections with Porphyromonas gingivalis, or introduction of its lipopolysaccharide (LPS), in various mouse models has demonstrated the development of key neuropathological hallmark lesions defining AD. These are extracellular amyloid-beta plaques, phosphorylated tau, neurofibrillary tangles, widespread acute and chronic inflammation, blood–brain barrier defects together with the clinical phenotype showing impaired learning and spatial memory. Live P. gingivalis and its LPS (commercial or from ‘microbullets’) are powerful peripheral and intracerebral inflammatory signalling initiators, and this has direct implications on memory and lesion development. Maintaining a healthy oral microbiome and managing periodontal disease with regular surveillance and good oral hygiene throughout life is likely to reduce the unnecessary burden of AD in some individuals.
Highlights
Periodontitis is a highly prevalent oral disease in humans affecting nearly 50% of the population worldwide [1]
This study reported Alzheimer’s disease (AD) like behaviour following P. gingivalis ATCC 33277T LPS introduction in mice, and above all demonstrated intracellular release of Aβ according to the hypothesis of Hook et al [46] via the regulated secretory vesicle pathway mediated by cathepsin B (Figure 3), which consolidated the causative relationships of P. gingivalis with AD [55]
P. gingivalis infections and its LPS appear to be closely associated with the development of the sporadic form of AD
Summary
Periodontitis is a highly prevalent oral disease in humans affecting nearly 50% of the population worldwide [1]. KEYWORDS Alzheimer’s disease; chronic periodontitis; cause; infection; P. gingivalis; lipopolysaccharide risk factor; intervention Behavioural testing demonstrated that the cognitive function was significantly impaired in periodontitis-induced APP-Tg mice compared to the sham-infected group.
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