PET Imaging of Amyloid in the HIV Brain

描述（由申请人提供）：这是R21 MH 072529 -01赠款的修订提案。所有三位评审员都同意，拟议的研究是重要的和创新的，可能会提供有关疾病新机制的更多信息，但对薄弱的临床研究，HAART的艾滋病毒患者数量不足以及Becker博士对该项目的贡献表示担忧。我们回应了批评，重新设计了临床研究（见我们的新引言）。近年来，接受高效抗逆转录病毒治疗（HAART）的人类免疫缺陷病毒（HIV）阳性患者的总体临床状况显着改善。现在人们认为，更积极的抗病毒疗法可能对大脑产生长期影响。我们认为，HAART长期存活者的寿命延长与长期高胰岛素血症状态相结合，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。在一项对162例病例的初步研究中，我们对尸检脑组织进行了免疫细胞化学，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）配体可用于体内测试我们的假设。SA#1：使用新型PET配体（PIB）完成艾滋病患者中Abeta沉积的横断面分析。评价年龄和HAART时间对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。我们建议，PET成像可以检测到早期的迹象，大脑退化的HIV感染的HAART患者，并可能监测脑病理与it. Since轻微的认知功能障碍的发病率可能会增加，Aa作为一个致病因素的研究将是有用的，在设计未来的NeuroAIDS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.