Inflammation and Alzheimer's disease: Possible role of periodontal diseases

Department of Periodontology and Implant Dentistry, College of Dentistry, New York University, New York, NY, USA.
Alzheimer's & dementia: the journal of the Alzheimer's Association (Impact Factor: 17.47). 07/2008; 4(4):242-50. DOI: 10.1016/j.jalz.2007.08.004
Source: PubMed

ABSTRACT The molecular and cellular mechanisms responsible for the etiology and pathogenesis of Alzheimer's disease (AD) have not been defined; however, inflammation within the brain is thought to play a pivotal role. Studies suggest that peripheral infection/inflammation might affect the inflammatory state of the central nervous system. Chronic periodontitis is a prevalent peripheral infection that is associated with gram-negative anaerobic bacteria and the elevation of serum inflammatory markers including C-reactive protein. Recently, chronic periodontitis has been associated with several systemic diseases including AD. In this article we review the pathogenesis of chronic periodontitis and the role of inflammation in AD. In addition, we propose several potential mechanisms through which chronic periodontitis can possibly contribute to the clinical onset and progression of AD. Because chronic periodontitis is a treatable infection, it might be a readily modifiable risk factor for AD.

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    • "Systemic inflammation and infections could worsen a number of CNS disorders [26] [43]. Among the common chronic inflammatory disorders in adults, much attention has been paid to the periodontitis as the pathogenesis of CNS disorders, including AD [13] [15] [44]. The increase in macrophage-derived TNF-í µí»¼ and IL-1í µí»½ in the circulation during periodontitis [39] [40] also supports the idea that chronic periodontitis is involved in the pathogenesis of systemic inflammatory diseases, including atherosclerosis, cardiovascular disease, and diabetes [10] [11] [12]. "
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    ABSTRACT: We report here that the leptomeningeal cells transduce inflammatory signals from peripheral macrophages to brain-resident microglia in response to Porphyromonas gingivalis (P.g.) LPS. The expression of Toll-like receptor 2 (TLR2), TLR4, TNF- α , and inducible NO synthase was mainly detected in the gingival macrophages of chronic periodontitis patients. In in vitro studies, P.g. LPS induced the secretion of TNF- α and IL-1 β from THP-1 human monocyte-like cell line and RAW264.7 mouse macrophages. Surprisingly, the mean mRNA levels of TNF- α and IL-1 β in leptomeningeal cells after treatment with the conditioned medium from P.g. LPS-stimulated RAW264.7 macrophages were significantly higher than those after treatment with P.g. LPS alone. Furthermore, the mean mRNA levels of TNF- α and IL-1 β in microglia after treatment with the conditioned medium from P.g. LPS-stimulated leptomeningeal cells were significantly higher than those after P.g. LPS alone. These observations suggest that leptomeninges serve as an important route for transducing inflammatory signals from macrophages to microglia by secretion of proinflammatory mediators during chronic periodontitis. Moreover, propolis significantly reduced the P.g. LPS-induced TNF- α and IL-1 β production by leptomeningeal cells through inhibiting the nuclear factor- κ B signaling pathway. Together with the inhibitory effect on microglial activation, propolis may be beneficial in preventing neuroinflammation during chronic periodontitis.
    Mediators of Inflammation 12/2013; 2013:407562. DOI:10.1155/2013/407562 · 2.42 Impact Factor
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    • "Lastly, associations between periodontal disease and other diseases in living populations can exist because the body responds to the presence of bacteria and bacterial antigens in the oral cavity and in the bloodstream through the production of proinflammatory immune cytokines, such as interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-a), which can have systemic or distant effects (Loos, 2005; Moutsopoulos and Madianos, 2006; Spahr et al., 2006). These effects include causing or accelerating atherogenesis (the formation of plaques within arteries) and thus contributing to cardiovascular disease (Amabile et al., 2008; Kamer et al., 2008; Watts et al., 2008), affecting cell growth control and leading to carcinogenesis (Meyer et al., 2008), or priming microglial cells and other factors associated with Alzheimer's disease pathology (Watts et al., 2008). "
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    ABSTRACT: Numerous studies have demonstrated significant associations between periodontal disease and many other diseases in living populations, and some studies have shown that individuals with periodontal disease are at elevated risks of mortality. Recent analysis of a medieval skeletal sample from London has also shown that periodontal disease was associated with increased risks of mortality in the past. This study examines whether periodontal disease is associated with periosteal lesions in a skeletal sample from the urban St. Mary Graces cemetery (n = 265) from medieval London. The results reveal a significant association between periodontal disease and periosteal lesions in the St. Mary Graces sample (i.e., individuals with periodontal disease were also likely to have periosteal lesions), and the association between the two is independent of age. The association between the two pathological conditions might reflect underlying reduced immune competence and thus heightened susceptibility to pathogens that cause periodontal disease or periosteal lesions, exposure to an environmental factor, or underlying heightened inflammatory responses.
    American Journal of Physical Anthropology 12/2011; 146(4):609-18. DOI:10.1002/ajpa.21622 · 2.51 Impact Factor
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    • "The interaction between periodontopathic bacteria and the host response may result in significant systemic inflammation characterized by production of inflammatory molecules including IL-1β, IL-6, and TNF-α (D'Aiuto et al., 2004). Therefore, periodontal bacteria and systemic inflammatory molecules may contribute to brain inflammation that characterizes AD and affects its expression (Kamer et al., 2008a). Support for this hypothesis comes from earlier studies that used dark field microscopy, molecular and immunological techniques to identify spirochetes including Treponema species (periodontal pathogens) with higher frequency in the brains of AD patients compared to non-AD subjects (Miklossy, 1993; Riviere et al., 2002). "
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    ABSTRACT: The associations of inflammation/immune responses with clinical presentations of Alzheimer's disease (AD) remain unclear. We hypothesized that TNF-alpha and elevated antibodies to periodontal bacteria would be greater in AD compared to normal controls (NL) and their combination would aid clinical diagnosis of AD. Plasma TNF-alpha and antibodies against periodontal bacteria were elevated in AD patients compared with NL and independently associated with AD. The number of positive IgG to periodontal bacteria incremented the TNF-alpha classification of clinical AD and NL. This study shows that TNF-alpha and elevated numbers of antibodies against periodontal bacteria associate with AD and contribute to the AD diagnosis.
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