Prostaglandins & Oxidative Damage in ADAPT Participants

超出所提供的空间。几项大型流行病学研究表明，服用非甾体抗炎药（NSAIDs）超过2年的老年人阿尔茨海默病（AD）的发病率显著降低。然而，非甾体抗炎药在已确诊AD患者中的临床试验未能显示出疗效。这导致了一种假设，即非甾体抗炎药抑制了对AD起始至关重要的病理过程，这些过程可能与环氧化酶和随后的前列腺素（PG）产生的抑制有关。我们建议通过量化参加阿尔茨海默病抗炎预防试验（ADAPT）的受试者的内源性类二十烷酸生成来验证这一假设，该试验是nia赞助的一项关于非甾体抗炎药预防AD的研究。具体而言，我们将1)确定选择性和非选择性非甾体抗炎药在全身和中枢神经系统中抑制P - G减少的定量b标记物水平的功效；2)确定非甾体抗炎药对全身和中枢神经系统氧化损伤定量生物标志物水平的抑制作用；3) PG生成和氧化损伤的生物标志物水平变化与ADAPT测定的认知能力下降率相关。我们已经开发了高度准确和精确的质谱分析来定量PG、PG代谢物和脂质过氧化产物，并在我们的实验室常规进行这些分析。这些研究将为非甾体抗炎药预防AD的机制提供重要的见解。网站性能 ======================================== 节结束 ===========================================

EXCEED THE SPACE PROVIDED. Several large epidemiological studies have associated a profound reduction in the incidence of Alzheimer's Disease (AD) in older individuals who took non-steroidal anti-inflammatory drugs (NSAIDs) for longer than 2 years. However, clinical trials of NSAIDs in patients with established AD failed to show efficacy. This has led to the hypothesis that NSAIDs suppress pathologic processes critical to the initiation of AD and that these processes may be related to inhibition of the cyclooxygenase enzymes and subsequent prostaglandin (PG) production. We propose to test this hypothesis by quantifying endogenous eicosanoid production in subjects enrolled in the Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT), an NIA-sponsored study of NSAIDs in the prevention of AD. Specifically, we will 1) determine the efficacy of selective and non- selective NSAIDs t o suppress 1 evels o f quantitative b iomarkers o f P G p reduction systemically and in t he central nervous system of ADAPT participants; 2) determine the efficacy of NSAIDs to suppress levels of quantitative biomarkers of oxidative damage systemically and in the central nervous system of ADAPT participants; and 3) correlate changes in the levels of biomarkers of PG production and oxidative damage with rates of cognitive decline as determined in ADAPT. We have developed highly accurate and precise mass spectrometric assays to quantify PGs, PG metabolites, and lipid peroxidation products and are routinely performing these assays in our laboratory. These studies will provide important insights into the mechanisms by which NSAIDs prevent AD. PERFORMANCE SITE ========================================Section End===========================================