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

该项目将研究神经影像学、血液和脑脊液来测量与阿尔茨海默病相关的神经变性。很少有研究通过结合信息丰富的神经成像和周围生物标志物来提供“生物标记”，以改善早期诊断和治疗监测，集中在同一受试者的神经退行性疾病的多种测量方法上。神经影像学研究将包括使用淀粉样斑块探针（PIB）、淀粉样斑块和缠结tau探针（FDDNP）的PET扫描，以及髓磷脂和白质束完整性的MRI测量。血浆测量信号蛋白和脑脊液（CSF）蛋白水平

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.