ALZHEIMERS DISEASE: EFFECTS OF ORAL INFECTION INFLAMMATION AND DISEASE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Alzheimer?s Disease: Effects of Oral Infection, Inflammation, and Disease Pamela Stein, DMD (Anatomy & Neurobiology, College of Medicine); Mentors: M. John Novak, David Wekstein, PhD (Associate Director, Sanders-Brown Aging Center) The characteristics of periodontal disease are a Gram negative infection, a local and systemic inflammatory response involving neutrophils, monocytes/macrophages, and lymphocytes, cytokine mediated regulation of the inflammatory response and cellular and extracellular pathology that results in loss of function of the affected area. Current research suggests that many of the same mechanisms are apparent in pathologically affected sites in AD. A Gram negative infection with Chlamydia pneumoniae has been implicated in the etiology of AD and activation of the resident macrophages of the brain, microglia, is a feature. Recent, pilot, prospective studies have indicated that patients with AD who have other systemic infections, demonstrate cognitive impairment that continues for at least 2 months after resolution of the infection and that the impairment is preceded by elevated serum levels of IL-1? ?. In addition, significant evidence is accruing to implicate cytokines in the etiology of brain pathology. The ability of circulating Gram negative organisms to activate inflammatory systems in the brain that may lead to pathologic changes, has been highlighted recently by the identification of specific receptors for formylated peptides on monocytes and microglia. These receptors are specific for Gram negative organisms and support the concept that Gram negative infection can initiate inflammatory and pathologic changes in the brain. In the current study we are working with The Sanders Brown Center on Aging to recruit subjects to test our hypothesis that older adults with a life history of exposure to extensive oral infection are at higher risk for developing Alzheimer?s disease than older adults who have maintained minimal levels of oral infection. Methods for testing our hypothesis include (1) characterizing the prevalence, extent and severity of periodontal disease in a population of patients with Alzheimer?s disease (AD) when compared to age, race, and sex matched controls (2) characterizing the subgingival microbial ecology in patients with AD and controls to determine if specific microbial characteristics are associated with adverse outcomes and (3) determining if patients with AD and periodontitis have elevated levels of circulating inflammatory mediators compared to patients with AD and no periodontitis and non-AD controls. Since the approval and funding of this pilot project, we have made considerable progress in obtaining IRB approval, establishing collaborative arrangements with the Sanders Brown investigators, and developing case report forms. We are now ready to enroll our first subject in June, 2005.