Can oral infection be a risk factor for Alzheimer's disease?

Abstract

Alzheimer's disease (AD) is a scourge of longevity that will drain enormous resources from public health budgets in the future. Currently, there is no diagnostic biomarker and/or treatment for this most common form of dementia in humans. AD can be of early familial-onset or sporadic with a late-onset. Apart from the two main hallmarks, amyloid-beta and neurofibrillary tangles, inflammation is a characteristic feature of AD neuropathology. Inflammation may be caused by a local central nervous system insult and/or by peripheral infections. Numerous microorganisms are suspected in AD brains ranging from bacteria (mainly oral and non-oral Treponema species), viruses (herpes simplex type I), and yeasts (Candida species). A causal relationship between periodontal pathogens and non-oral Treponema species of bacteria has been proposed via the amyloid-beta and inflammatory links. Periodontitis constitutes a peripheral oral infection that can provide the brain with intact bacteria and virulence factors and inflammatory mediators due to daily, transient bacteremias. If and when genetic risk factors meet environmental risk factors in the brain, disease is expressed, in which neurocognition may be impacted, leading to the development of dementia. To achieve the goal of finding a diagnostic biomarker and possible prophylactic treatment for AD, there is an initial need to solve the etiological puzzle contributing to its pathogenesis. This review therefore addresses oral infection as the plausible etiology of late-onset AD (LOAD).

Cerebral Oxidative Stress and Microvasculature Defects in TNF-α Expressing Transgenic and Porphyromonas gingivalis-Infected ApoE–/– Mice

“…In the ageing brain and during AD, the APOE4 genetic susceptibility further capable of increasing the possibility of recurrent infections, leakage of plasma proteins, ROS and metallic ion production (iron from erythrocyte death), adding to a growing pool of oxidative stress mediators within the brain. Furthermore, oral and extra-oral bacteria are documented to be present within AD brains [10], where these are likely to promote additional ROS generation and host tissue damage. During chronic periodontal infection, oral pathobionts, such as Porphyromonas gingivalis (P. gingivalis), drive the host's immunoinflammatory responses towards elevated levels of pro-inflammatory cytokines, such as tumour necrosis factor-α (TNF-α), interleukin (IL) IL-1β and IL-6; leading to elevated oxidative stress [11].…”

Apolipoprotein E Related Co-Morbidities and Alzheimer’s Disease

“…Poor oral hygiene, and genetic susceptibility with apoε and low-density lipoprotein receptor-related protein 5 (LRP5) polymorphisms and in the neuropeptide Y (NPY) gene in aggressive periodontitis in the susceptible male host (whereas it is downregulated in female subjects) have been identified suggesting a sex-specific effect of genetic variation of NPY on PD [52]. Genetic polymorphisms would appear to be a risk factor in developing PD, which subsequently associates with remote organ metabolic states such as diabetes [53], and inflammatory pathologies such as vascular disease(s) [54,55], and AD [56][57][58][59][60][61], and others that are out of the scope of this review.…”

“…Infections and inflammation induce dyslipidaemia [14], and AD pathogeneses is not complete without documenting chronic peripheral infections [61]. These include Chlamydophila pneumoniae [C. pneumoniae], T. denticola, P. gingivalis which are also found in atheroma plaque tissues [93][94][95][96][97] and in AD brains [56,60,125], herpes simplex virus type I [126], and several species of spirochetes of which the well cited ones are T. denticola [56] and Borrelia burgdorferi [127].…”

“…As the susceptibility gene clearly requires an environmental risk factor for the expression of disease, avoidance of risk would be one therapeutic solution. For example, it is documented that not everyone with the hetero/homogeneous inheritance of apoε4 will result in manifesting diabetes, vascular diseases and AD [8,148], and if this risk factor is an oral infection, (56,60,61) as supported by the ApoE −/− mice induced with PD studies [70-73, 75, 132], then there is a therapeutic window for the related co-morbid states to modify the course of disease by adoption of healthy lifestyles and promotion of awareness about important early warning signs of serious health conditions by regular dental visits. …”

Porphyromonas gingivalis infection in gestational diabetes mellitus and survival in tobacco smokers.

“…This species was found in 85.75% of subgingival plaque samples from patients with chronic periodontitis [58]. Colonization by P. gingivalis is also associated with some systemic diseases, including cardiovascular diseases, rheumatoid arthritis, and Alzheimer's disease [59][60][61]. Its occurrence is higher in subjects with chronic periodontitis compared to periodontally healthy subjects [62,63].…”