BRAIN PET, MRI AND PERIPHERAL BIOMARKERS IN ALZHEIMER'S DISEASE

阿尔茨海默病的脑 PET、MRI 和外周生物标志物

• 批准号: 8440502
• 负责人: GARY William SMALL
• 金额: $ 18万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-05 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8440502
• 关键词: BRAIN; PET; MRI; PERIPHERAL; BIOMARKERS

This project will study neuroimaging, blood, and CSF to measure neurodegeneration associated with AD. Few studies have focused on multiple measures of neurodegeneration in the same subjects by combining informative neuroimaging and peripheral biomarkers to provide a "biosignature," in order to improve early diagnosis and treatment monitoring. Neuroimaging studies will include PET scans using probes of amyloid plaques (PIB) and amyloid plaques and tau in tangles (FDDNP), and MRI measures of myelin and white matter tract integrity. Plasma measures of signaling proteins and cerebrospinal fluid (CSF) levels of proteins associated with plaques and tangles (e.g., elevated phosphorylated tau and low Abl-42) and demyelination (e.g., sulfatide) will also be obtained. The UCLA Clinical Core will recruit 80 subjects (40 AD patients and 40 older cognitively-intact controls), and the Center's Imaging and Biomarker Core will assist with data storage and analysis. All subjects will receive neuropsychological testing, scans, and blood tests (apolipoprotein E genotyping and plasma signaling proteins), and an estimated 50 will agree to lumbar punctures for CSF measures. We will test the following hypotheses: (1) Plasma signaling protein biomarkers will differentiate AD patients from controls. (2) CSF Ab and phosphorylated tau will differentiate AD patients from controls. Within the AD and control subject groups, CSF Ab biomarkers will correlate with PIB signals, while both Ab and phosphorylated tau CSF biomarkers will correlate with FDDNP signals. (3) MRI measures of myelin integrity will differentiate AD and control groups. We will also explore possible associations of these MRI measures with CSF sulfatide values. (4) While both FDDNP and PIB signals will differentiate AD from controls, binding patterns will differ. FDDNP will label regions predicted to show tangle as well as plaque deposition; PIB will label predicted plaque-rich regions. Within the AD and control groups, we will also explore correlations between cognitive measures and PET binding signals. We will explore research questions on how well a potential combined-measure or biosignature predicts clinical decline and whether stratifying subjects according to apolipoprotein E genotype influences findings. This project would lay the groundwork for better quantification and understanding of these critical neurodegenerative biomarkers.

该项目将研究神经影像、血液和脑脊液，以测量与 AD 相关的神经变性。很少有研究通过结合信息丰富的神经影像和外周生物标志物来关注同一受试者的神经退行性疾病的多种测量，以提供“生物印记”，以改善早期诊断和治疗监测。神经影像学研究将包括使用淀粉样斑块 (PIB) 和淀粉样斑块和 tau 蛋白缠结 (FDDNP) 探针进行 PET 扫描，以及髓磷脂和白质束完整性的 MRI 测量。血浆信号蛋白检测和脑脊液 (CSF) 蛋白水平 还可以获得与斑块和缠结（例如，磷酸化 tau 升高和 Abl-42 降低）和脱髓鞘（例如硫脑苷脂）相关的结果。加州大学洛杉矶分校临床核心将招募 80 名受试者（40 名 AD 患者和 40 名认知完整的老年对照），该中心的成像和生物标记核心将协助数据存储和分析。所有受试者都将接受神经心理学测试、扫描和血液测试（载脂蛋白 E 基因分型和血浆信号蛋白），估计有 50 名受试者同意腰椎穿刺以进行脑脊液测量。我们将测试以下假设：（1）血浆信号蛋白生物标志物将区分 AD 患者和对照组。 (2) CSF Ab 和磷酸化 tau 蛋白可将 AD 患者与对照组区分开来。在 AD 和对照受试者组中，CSF Ab 生物标志物将与 PIB 信号相关，而 Ab 和磷酸化 tau CSF 生物标志物将与 FDDNP 信号相关。 (3) 髓磷脂完整性的 MRI 测量将区分 AD 组和对照组。我们还将探讨这些 MRI 测量值与脑脊液硫苷脂值之间的可能关联。 (4) 虽然 FDDNP 和 PIB 信号都会将 AD 与对照区分开来，但结合模式会有所不同。 FDDNP 将标记预计会出现缠结和斑块的区域 沉积； PIB 将标记预测的斑块丰富区域。在 AD 组和对照组中，我们还将探索认知测量和 PET 结合信号之间的相关性。我们将探讨以下研究问题：潜在的综合测量或生物特征如何预测临床衰退，以及根据载脂蛋白 E 基因型对受试者进行分层是否会影响研究结果。该项目将为更好地量化和理解这些关键的神经退行性生物标志物奠定基础。