Abstract

Alzheimer’s disease (AD) is the most prevalent form of dementia in the elderly population, representing a global public health priority. Despite a large improvement in understanding the pathogenesis of AD, the etiology of this disorder remains still unclear, and no current treatment is able to prevent, slow, or stop its progression. Thus, there is a keen interest in the identification and modification of the risk factors and novel molecular mechanisms associated with the development and progression of AD. In this context, it is worth noting that several findings support the existence of a direct link between neuronal and non-neuronal inflammation/infection and AD progression. Importantly, recent studies are now supporting the existence of a direct relationship between periodontitis, a chronic inflammatory oral disease, and AD. The mechanisms underlying the association remain to be fully elucidated, however, it is generally accepted, although not confirmed, that oral pathogens can penetrate the bloodstream, inducing a low-grade systemic inflammation that negatively affects brain function. Indeed, a recent report demonstrated that oral pathogens and their toxic proteins infect the brain of AD patients. For instance, when AD progresses from the early to the more advanced stages, patients could no longer be able to adequately adhere to proper oral hygiene practices, thus leading to oral dysbiosis that, in turn, fuels infection, such as periodontitis. Therefore, in this review, we will provide an update on the emerging (preclinical and clinical) evidence that supports the relationship existing between periodontitis and AD. More in detail, we will discuss data attesting that periodontitis and AD share common risk factors and a similar hyper-inflammatory phenotype.

Highlights

  • Alzheimer’s disease (AD) is a neurodegenerative disorder affecting millions of people worldwide, with a frequency that is rapidly rising as the life expectancy increases and the world population becomes older (Brookmeyer et al, 2002, 2007; SosaOrtiz et al, 2012; Alzheimer’s Association., 2016)

  • The current debate focuses on one main question: what comes first? Some studies have demonstrated that people with periodontitis present a major risk of developing AD (Chen et al, 2017); other reports suggest that those with AD or dementia suffer from inadequate oral health, stemming from cognitive decline, and are, more likely to develop periodontitis (Tada et al, 2006; Gonsalves et al, 2008; Maldonado et al, 2018)

  • While waiting for the publication of the trial outcome, we can ascertain, with no additional hesitation, that a more careful dental treatment effectively improves the quality of life/cognitive impairment of patients with mild AD (Rolim et al, 2014)

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Summary

Introduction

Alzheimer’s disease (AD) is a neurodegenerative disorder affecting millions of people worldwide, with a frequency that is rapidly rising as the life expectancy increases and the world population becomes older (Brookmeyer et al, 2002, 2007; SosaOrtiz et al, 2012; Alzheimer’s Association., 2016). Many reports are supporting the role of inflammation as a significant pathological driver of AD development and cognitive decline, with evidence that communication between the brain and peripheral immune systems exists (Goldeck et al, 2016; Cao and Zheng, 2018; Alexandraki et al, 2019; Long and Holtzman, 2019; Tejera et al, 2019). Of note is that this risk was almost eliminated in patients treated with antiherpetics (Chen et al, 2018; Tzeng et al, 2018; Long and Holtzman, 2019)

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