ADRD plasma biomarkers and cognition in aging women with and without HIV infection

摘要 慢性艾滋病毒感染是一个世纪的现象，由于高效的药物称为抗逆转录病毒 治疗（ART）。由于抗逆转录病毒疗法，艾滋病毒感染者在年龄较大时可以活到更大的年龄。 阿尔茨海默病和相关痴呆症（ADRD）的风险。这是前所未有的。感染者 艾滋病毒感染者也会遇到与艾滋病毒感染有关的认知问题和更多的神经系统疾病。 特别是女性，由于肥胖和吸烟以及某些类型的ART， 会增加血管风险高血管风险与ADRD相关。确定血液生物标志物， 告诉我们一个人患ADRD的风险是非常重要的。一个简单的血液测试也会帮助我们更好地 了解ADRD大脑病理，或导致记忆丧失和临床AD的变化。两个这样 病理学与大脑中的异常蛋白质有关，称为淀粉样蛋白和tau蛋白，第三种称为 神经退化或脑细胞死亡。血管疾病（血管和循环变化）也是 共同由于感染艾滋病毒的妇女已经处于高风险之中，因此探索 神经退行性变和血管健康对于理解艾滋病毒感染和 ADRD，以及ADRD之前的认知障碍。候选人，最先进的血液ADRD 生物标志物包括称为Abeta-40和Abeta 42的淀粉样蛋白（A）蛋白以及脑损伤的蛋白质标志物 称为总tau（t-tau）、磷酸化tau（p-tau）和神经丝轻链（NFL）。这些生物标志物 通常在脑脊髓液中测量，脑脊髓液是一种浸泡大脑的水状液体。最近的研究表明， 这些生物标志物的血液水平可以反映在脑脊液中观察到的水平， 发生在AD患者中的变化，例如由于神经细胞死亡导致的脑萎缩，以及其他可能 是由血管疾病引起的我们有很大的机会来探索这些ADRD的重复措施 生物标志物Abeta-40、Abeta-42、t-tau、p-tau和NFL，与390例患者10年以上的认知相关 至少45岁的女性-260名艾滋病毒感染者和130名对照组 未感染的女性这是一个年龄，如果AD发展，Abeta和tau最初会开始积累 慢慢地，静静地。我们建议使用来自MACS/WIHS联合队列研究的历史数据 （妇女、社区和社会服务部）妇女、家庭和保健服务妇女。2019年，WIHS女性的平均年龄为53岁， 人口统计学、临床、神经和血管结局、其他疾病和风险因素以及ART使用， 以及随着时间的推移收集的储存血液。2009年，WIHS开始每两年进行一次认知测量， 不同类型的思维，以及全球思维。我们将首次将ADRD血液生物标志物与 随着时间的推移，艾滋病毒感染和未感染艾滋病毒的妇女的认知。这将促进我们对大脑的理解 艾滋病病毒中的衰老

ABSTRACT Chronic HIV infection is a 21st century phenomenon due to highly-effective medications called antiretroviral therapies (ART). Because of ART, people living with HIV infection are surviving to older ages when they are at risk for Alzheimer’s Disease and Related Dementias (ADRD). This has never been seen before. People living with HIV also experience cognitive problems and more nervous system illnesses related to the HIV infection. Women, in particular, are at higher vascular risk due to obesity and smoking, as well as certain types of ART that increase vascular risk. High vascular risk is related to ADRD. Identification of blood biomarkers that can tell us something about a person’s risk for ADRD is very important. A simple blood test will also help us better understand ADRD brain pathologies, or changes that lead to memory loss and clinical AD. Two of these pathologies are related to abnormal proteins in the brain, called amyloid and tau, and a third, is called neurodegeneration, or brain cell death. Vascular disease (blood vessel and circulation changes) is also common. Because women with HIV infection are already at high risk, exploring biomarkers of neurodegeneration and vascular health is paramount to understanding associations between HIV infection and ADRD, as well as cognitive impairments that come before ADRD. Candidate, state-of-the-art blood ADRD biomarkers include amyloid (A) proteins called Abeta-40 and Abeta42, and protein markers of brain damage called total tau (t-tau), phospho-tau (p-tau), and NeuroFilament Light chain (NFL). These biomarkers are usually measured in cerebrospinal fluid, the watery fluid that bathes the brain. Recent studies suggest that blood levels of these biomarkers may mirror levels observed in cerebrospinal fluid and are related to brain changes that occur in AD patients, such as brain shrinking due to nerve cell death, and other changes that may result from vascular disease. We have the great opportunity to explore repeated measures of these ADRD biomarkers Abeta-40, Abeta-42, t-tau, p-tau, and NFL, in association with cognition over 10 years in 390 women, who are at least 45 years old - 260 surviving with HIV infection and a comparison group of 130 uninfected women. This is an age when if AD were to develop, Abeta and tau would initially start to accumulate slowly and silently. We propose to use historical data from the MACS/WIHS Combined Cohort Study (MWCCS) WIHS women. In 2019, WIHS women were average 53 years old with measures of social, demographic, clinical, neurological and vascular outcomes, other illnesses, and risk factors, and ART use, as well as stored blood collected over time. In 2009, WIHS began cognitive measures every 2 years to measure different types of thinking, as well as global thinking. For the first time, we will link ADRD blood biomarkers to cognition over time in women with and without HIV infection. This will advance our understanding of brain aging in HIV.