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

该项目将研究神经成像、血液和脑脊液，以测量与AD相关的神经退行性变。很少有研究集中于同一受试者的多种神经变性测量方法，方法是将信息丰富的神经成像和外周生物标记物结合起来提供“生物签名”，以改善早期诊断和治疗监测。神经成像研究将包括使用淀粉样斑块(PIB)和淀粉样斑块和缠结中的tau(FDDNP)探针的PET扫描，以及髓鞘和白质束完整性的MRI测量。血浆信号蛋白和脑脊液蛋白质水平的测定 与斑块和缠结相关的(例如，升高的磷酸化tau和低的Abl-42)和脱髓鞘(例如，硫脂)也将被获得。加州大学洛杉矶分校临床核心中心将招募80名受试者(40名AD患者和40名认知正常的老年人)，该中心的成像和生物标记物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人将同意腰椎穿刺术进行脑脊液检查。我们将检验以下假设：(1)血浆信号蛋白生物标记物将区分AD患者和对照组。(2)脑脊液抗体和磷酸化tau有助于区分AD患者和对照组。在AD和对照组中，脑脊液抗体生物标记物将与PIB信号相关，而抗体和磷酸化tau-CSF生物标记物将与FDDNP信号相关。(3)髓鞘完整性的MRI测量将区分AD组和对照组。我们还将探索这些MRI测量方法与脑脊液硫脂值的可能关联。(4)虽然FDDNP和PIB信号都将AD与对照区分开来，但结合模式将不同。FDDNP将标记预计会显示缠结和斑块的区域 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。我们将探索潜在的联合测量或生物特征对临床下降的预测效果如何，以及根据载脂蛋白E基因对受试者进行分层是否会影响结果的研究问题。该项目将为更好地量化和了解这些关键的神经退行性生物标志物奠定基础。

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.