Periodontal microorganisms and Alzheimer disease – A causative relationship?

Abstract

In the initiation or exacerbation of Alzheimer disease, the dissemination of oral microorganisms into the brain tissue or the low‐level systemic inflammation have been speculated to play a role. However, the impact of oral microorganisms, such as Porphyromonas gingivalis, on the pathogenesis of Alzheimer disease and the potential causative relationship is still unclear. The present review has critically reviewed the literature by examining the following aspects: (a) the oral microbiome and the immune response in the elderly population, (b) human studies on the association between periodontal and gut microorganisms and Alzheimer disease, (c) animal and in vitro studies on microorganisms and Alzheimer disease, and (d) preventive and therapeutic approaches. Factors contributing to microbial dysbiosis seem to be aging, local inflammation, systemic diseases, wearing of dentures, living in nursing homes and no access to adequate oral hygiene measures. Porphyromonas gingivalis was detectable in post‐mortem brain samples. Microbiome analyses of saliva samples or oral biofilms showed a decreased microbial diversity and a different composition in Alzheimer disease compared to cognitively healthy subjects. Many in‐vitro and animal studies underline the potential of P gingivalis to induce Alzheimer disease‐related alterations. In animal models, recurring applications of P gingivalis or its components increased pro‐inflammatory mediators and β‐amyloid in the brain and deteriorated the animals' cognitive performance. Since periodontitis is the result of a disturbed microbial homoeostasis, an effect of periodontal therapy on the oral microbiome and host response related to cognitive parameters may be suggested and should be elucidated in further clinical trials.

Interconnection of periodontal disease and comorbidities: Evidence, mechanisms, and implications

“…Clinical and microbial markers of periodontal disease have been associated with the incidence and mortality of Alzheimer disease. According to the review of the relevant literature by Eick and colleagues, 44 this association might, at least in part, be causal and two general mechanisms have been proposed: Direct effects of oral microorganisms infiltrating the brain and the non‐mutually exclusive mechanism that periodontitis may aggravate Alzheimer disease pathology by increasing systemic inflammation. The authors focus mainly on the first mechanism.…”

Interdisciplinary Approaches to Deal with Alzheimer’s Disease—From Bench to Bedside: What Feasible Options Do Already Exist Today?

“…Although there is a growing interest in the effects of dental therapy on the occurrence and progression of AD, dentistry still has a minor role in the multidisciplinary context. Despite interrelated biochemical processes in intraoral inflammation and AD [ 349 , 355 ], there are few clinical studies investigating the effectiveness of oral treatment approaches in AD. Difficulties in recruitment include ethical issues, the health status of people with disabilities, lack of compliance, required involvement of relatives, treatment limitations, and economic issues [ 351 , 396 , 414 ].…”

“…Gingipains in particular are thought to be highly relevant with regard to the initiation of the AD process and have therefore also led to the development of a new drug therapy approach—a gingipain inhibitor [ 353 ]. However, such a compound (COR388), which was later clinically tested in a phase II/III trial, failed to lead to therapeutic success and was discontinued—also due to side effects [ 354 , 355 ].…”

Design, Docking, Synthesis and Biological Evaluation of Novel Nicotinohydrazone Derivatives as Potential Butyrylcholinesterase Enzyme Inhibitor

“…One of the causes of these symptoms is the disorders that occur with the decrease of the neurotransmitter acetylcholine (ACh), which is associated with cognitive functions. Studies show that AD occurs as a multifactorial disease, however, AD has two distinctive pathologies: Aβ accumulation and neurofibrillary tangles containing hyperphosphorus and tau [9a–d] . In addition, it has been reported in some studies that amyloid deposition can be seen in the brain tissue before the onset of clinical symptoms [10] …”