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

感染和未感染 HIV 的老年女性的 ADRD 血浆生物标志物和认知

基本信息

批准号：
10119421
负责人：
DEBORAH R. GUSTAFSON
金额：
$ 40.1万
依托单位：
SUNY DOWNSTATE MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-04-01 至 2026-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10119421
关键词：
Address Age Aging Alleles Alzheimer&apos s Disease Alzheimer&apos s disease related dementia Alzheimer&apos s disease risk Alzheimer’s disease biomarker Amyloid Amyloid Proteins Amyloid beta-42 Amyloid beta-Protein Area Attention Biological Markers Blood Blood Circulation Blood Tests Blood Vessels Brain Brain Injuries Brain Pathology Brain imaging CD4 Lymphocyte Count CD8B1 gene Cell Death Cerebrospinal Fluid Chronic Clinical Cognition Cognitive Cohort Studies Craniocerebral Trauma Data Early Diagnosis Effectiveness Enrollment Event Future Genotype HIV HIV Infections HIV antiretroviral HIV-associated neurocognitive disorder Health Hyperlipidemia Hypertension Impaired cognition Intervention Investigation Language Lead Learning Light Link Liquid substance Longitudinal Studies Magnetic Resonance Imaging Measures Memory Memory Loss Morbidity - disease rate National Institute on Aging Nerve Degeneration Nervous system structure Neurologic Obesity Outcome Participant Pathology Patient Self-Report Patients Penetration Peripheral Nervous System Diseases Persons Pharmaceutical Preparations Plasma Population Positron-Emission Tomography Proteins Recording of previous events Research Risk Risk Factors Role Short-Term Memory Smoking Specimen Speed Stroke Thinking Time Traumatic Brain Injury Vascular Diseases Viral Load result White Matter Hyperintensity Woman Women’s Interagency HIV Study abeta oligomer age group aging brain antiretroviral therapy apolipoprotein E-4 base brain cell clinically relevant cognitive change cognitive performance comorbidity comparison group depressive symptoms executive function experience health disparity high risk information processing neurofilament neuron loss neuropathology peripheral blood protein biomarkers risk variant social sociodemographics tau Proteins tau-1 therapy adherence unhealthy lifestyle

项目摘要

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.

抽象的慢性艾滋病毒感染是一种21世纪现象，因为高效的药物称为抗逆转录病毒治疗（艺术）。由于艺术，感染艾滋病毒感染的人在阿尔茨海默氏病和相关痴呆症（ADRD）的风险。这从未见过。人们生活艾滋病毒还遇到认知问题和与艾滋病毒感染有关的更多神经系统疾病。尤其是妇女，由于肥胖和吸烟以及某些类型的艺术，妇女的血管风险更高增加血管风险。高血管风险与ADRD有关。可以识别可以告诉我们一些人的ADRD风险非常重要。简单的血液检查也将帮助我们更好了解ADRD的大脑病理或导致记忆力丧失和临床AD的变化。其中两个病理学与称为淀粉样蛋白和tau的大脑中的异常蛋白有关，三分之一称为神经变性或脑细胞死亡。血管疾病（血管和循环变化）也是常见的。因为感染艾滋病毒感染的女性已经处于高风险神经变性和血管健康对于理解HIV感染与 ADRD以及ADRD之前发生的认知障碍。候选人，最先进的血液Adrd 生物标志物包括称为Abeta-40和Abeta42的淀粉样蛋白（A）蛋白质，以及脑损伤的蛋白质标记物称为Total Tau（T-Tau），磷酸-TAU（P-TAU）和神经丝轻链（NFL）。这些生物标志物是通常在脑脊液中测量的水流体沐浴大脑。最近的研究表明这些生物标志物的血液水平可能反映在脑脊液中观察到的水平，并且与大脑有关 AD患者发生的变化，例如由于神经细胞死亡而导致的大脑萎缩，其他可能的变化可能由血管疾病引起的。我们有很好的机会来探索这些ADRD的重复措施生物标志物Abeta-40，Abeta-42，T-Tau，P-Tau和NFL与390年的认知合作10年妇女，至少45岁-260岁，患有艾滋病毒感染和130人的比较组未感染的妇女。这是一个年龄，如果要开发广告，Abeta和Tau最初将开始积累缓慢而默默地。我们建议使用Mac/WIHS组合研究的历史数据（MWCC）女性。 2019年，WIHS妇女平均有53岁的社会措施，人口统计，临床，神经和血管结局，其他疾病以及危险因素以及艺术使用，作为随着时间的流逝，储存的血液储存。 2009年，WIHS开始每2年开始认知措施来衡量不同类型的思维以及全球思维。我们第一次将Adrd Blood生物标志物与患有和没有艾滋病毒感染的女性的认知随着时间的流逝。这将提高我们对大脑的理解艾滋病毒衰老。