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（NSAID）超过2年的老年人的阿尔茨海默病（AD）发病率显著降低。然而，NSAID在已确诊AD患者中的临床试验未能显示疗效。这导致了以下假设，即NSAID抑制对AD起始至关重要的病理过程，并且这些过程可能与抑制环氧合酶和随后的前列腺素（PG）产生有关。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花生酸产生来验证这一假设，ADAPT是一项由NIA赞助的NSAID预防AD的研究。具体而言，我们将1）确定选择性和非选择性NSAID抑制ADAPT参与者全身和中枢神经系统中PG p减少的定量B生物标志物水平的功效; 2）确定NSAID抑制ADAPT参与者全身和中枢神经系统中氧化损伤的定量生物标志物水平的功效;和3）将PG产生和氧化损伤的生物标志物水平的变化与ADAPT中确定的认知下降速率相关联。我们开发了高度准确和精确的质谱分析方法来量化PG、PG代谢物和脂质过氧化产物，并在我们的实验室定期进行这些分析。这些研究将为了解NSAID预防AD的机制提供重要见解。性能现场=

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===========================================