There is ample neuropathololgic evidence to suggest that inflammation plays an important role in the progression, and possibly initiation of the disease processes that ultimately lead to Alzheimer?s disease (AD). However little is known about the inflammatory profile of cases compared to non-cases, and whether cases have a predisposition toward a more pro-inflammatory phenotype. The cases and controls are currently being recruited from the study population of the Gingko Baloba Trial to slow the progression towards dementia. The goal is 65 cases and 65 controls.? ? Celluar markers of the adaptive immune response? The primary function of Th1 T helper cells is to assist the generation of cell-mediated immunity. They secrete a set of cytokines that are generally considered proinflammatory, exemplified by Interferon-? (IFN-?) and IL-12. Th2 cells function to assist humoral immunity, i.e., the generation of immunoglobulin by B cells. Th2 cells secrete a set of cytokines considered at least in some contexts, as anti-inflammatory, such as IL-4 and IL-10. Many of these cytokines have been identified in the neuropathologic material harvested from the brains of AD cases (McGeer and McGeer, 2001). Epidemiologic studies also suggest raised levels of pro-inflammatory cytokines may increase the risk for AD (Schmidt et al., 2002). A recent study demonstrated a Th1-dominated immune response in cases of AD (Remarque et al., 2001). Further, the promising vaccines have been developed on the basis of a humoral immune response to amyloid-a, the putative toxic protein in AD (Schenk et al., 1999). ? ? Little is known about cellular phenotypes in AD. Dr. Russell Tracy (University of Vermont) and colleagues have developed a new technique to characterize Th1 and Th2 cells. Their studies suggest the Th1/Th2 ratio is a characteristic individual phenotype that has good reliability over time. Their studies have also demonstrated the feasibility in doing these measures in epidemiologic studies. We propose to conduct a pilot study to test this phenotype in cases of Alzheimer?s disease and controls recruited through the Geriatric Clinical Research Center (GCRC) at Wake Forest Medical School (WFMS). It is hypothesized that AD cases will have a pro-inflammatory phenotype compared to controls.
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