PET Imaging of Amyloid in the HIV Brain

描述(申请人提供)：这是R21 MH072529-01资助的修订方案。所有三位评审者都同意，拟议的研究具有重大意义和创新性，可能会提供有关新疾病机制的更多信息，但他们对薄弱的临床研究、接受HAART治疗的艾滋病毒患者数量不足以及贝克尔博士对这一项目的贡献表示担忧。我们对批评做出了回应，并重新设计了临床研究(参见我们的新介绍)。近年来，接受高效抗逆转录病毒疗法(HAART)治疗的人类免疫缺陷病毒(HIV)阳性患者的一般临床状况明显改善。现在人们认为，更积极的抗病毒疗法可能会对大脑产生长期影响。我们认为，在长期接受HAART的患者中，寿命的延长和高胰岛素状态的延长可能会增加他们在大脑中发生β淀粉样蛋白(Abeta)沉积的风险。在对162例尸检脑组织进行的初步研究中，我们发现HIV患者的大脑中存在丰富的β-淀粉样蛋白(Abeta)。匹兹堡大学(PIB)开发的一种新的正电子发射断层扫描(PET)配体可以用来在体内验证我们的假设。SA#1：使用一种新型的PET配体(PIB)完成对艾滋病患者Abeta沉积的横断面分析。评估年龄和HAART长度对Abeta沉积的影响。SA#2：研究HIV患者和对照组尸检脑组织中Abeta的区域和细胞分布。我们认为，PET成像可以在HAART上发现HIV感染患者脑变性的早期迹象，并可能监测与其相关的脑病理。由于轻微认知障碍的发生率可能会增加，因此将AA作为致病因素的研究将有助于设计未来的神经艾滋病研究。

DESCRIPTION (provided by applicant): This is a revised proposal of the R21 MH072529-01 grant. All three reviewers agreed that the proposed studies are significant and innovative and may provide additional information on new mechanisms of disease but there were concerns regarding the weak clinical studies, insufficient number of HIV patients on HAART and Dr. Becker's contribution to this project. We responded to the criticisms and re-designed the clinical study (see our new Introduction). In recent years, human immunodeficiency virus (HIV) positive patients under highly active anti-retroviral therapy (HAART) regimens show a markedly improved general clinical status. It is now believed that the more aggressive antiviral therapies could have a long-term impact on the brain. We propose that increased longevity combined with a prolonged hyper-insulinemic state in long-term survivors on HAART may increase their risk of developing beta-amyloid (Abeta) deposition in the brain. In a pilot study of 162 cases, using immunocytochemistry on autopsy brain tissues, we found abundant beta-amyloid (Abeta) in the brains of HIV patients. A new positron emission tomography (PET) ligand developed at the University of Pittsburgh (PIB) can be used to test our hypothesis in vivo. SA#1: Complete a cross-sectional analysis of Abeta deposition in AIDS patients using a novel-PET ligand (PIB). Evaluate the effects of age and length of HAART on Abeta deposition. SA#2: Study the regional and cellular distribution of Abeta in autopsy brain tissues from HIV patients and controls. We propose that PET imaging may detect early signs of brain degeneration in HIV infected patients on HAART and possibly monitor the brain pathology associated with it. Since the incidence of minor cognitive impairment will probably increase, studies of Aa as a pathogenic factor will be useful in designing future NeuroAIDS studies.