Longitudinal Imaging Biomarkers of Disease Progression in DLB

项目摘要/摘要 路易体痴呆是一种以路易体存在为特征的临床综合征 疾病(LBD)，但其他与阿尔茨海默病(AD)相关的病理在以下患者中也很常见 德意志银行。尽管这两种病理对临床疾病进展的影响并不完全 了解，许多DLB患者可能从同时针对AD和LBD相关的治疗中受益 病理过程。为了为DLB的这些临床试验做准备，我们需要强大和可靠的生物标志物 这可以跟踪疾病的进展，特别是LBD和AD相关病理的进展。 我们提出了多模式成像生物标记物的病理过程普遍存在于患者 用于检测疾病进展的DLB。我们建议建立一个纵向队列的DLB患者和 获取临床和多模式成像生物标记物数据以对纵向成像生物标记物建模 DLB中关于临床疾病进展的变化。在目标1中，我们建议确定是否 阿尔茨海默病相关多巴胺能损伤的单光子发射计算机断层扫描和高淀粉样蛋白-β检测AD的病理生理 PET上的沉积和MRI上的AD特征萎缩与临床发病率相关 在目标2中，我们将确定这些纵向的 影像生物标记物和临床结果的变化及其相关性受遗传、性别- 基于，和脑血管疾病相关的特征。在目标3中，我们将确定tau配体的模式 DLB中的AV-1451摄取与对照组的比较及其与影像变化率的关系 生物标记物与临床疾病进展。最后，我们将确定该病的病理基础。 尸检患者DLB中生物标记物的变化，这是验证影像的金标准 除了这些侧重于假设检验的目标外，我们还将对RFA-NS- 16-022通过采集全血、血浆、血清、脑脊液和尿液样本，临床和协调 神经影像数据纵向；DNA和外周血单核细胞来自一个前瞻性队列 DLB患者，并将他们提交给PDBP。

PROJECT SUMMARY / ABSTRACT Dementia with Lewy bodies (DLB) is a clinical syndrome characterized by the presence of Lewy body disease (LBD), but additional Alzheimer's disease (AD)-related pathology is also common in patients with DLB. Although the impact of each of these two pathologies on the clinical disease progression is not fully understood, many DLB patients may benefit from treatments that target both AD and LBD-related pathological processes. To prepare for these clinical trials in DLB, we need robust and reliable biomarkers that can track disease progression, particularly the progression of both LBD- and AD-related pathologies. We propose multi-modal imaging biomarkers of pathological processes commonly present in patients with DLB to detect disease progression. We propose to establish a longitudinal cohort of patients with DLB and acquire clinical and multi-modal imaging biomarker data to model the longitudinal imaging biomarker changes with respect to clinical disease progression in DLB. In Aim 1, we propose to determine whether LBD-related dopaminergic loss on SPECT, and AD pathophysiology measured with higher amyloid-β deposition on PET and AD-signature atrophy on MRI is associated with the rate of clinical disease progression, cognitive decline and survival in DLB; In Aim 2, we will determine whether these longitudinal changes in imaging biomarkers and clinical outcomes, and their associations are modified by genetic, sex- based, and cerebrovascular disease-related features. In Aim 3, we will determine the pattern of a tau ligand AV-1451 uptake in DLB compared to controls and its relationship to the rate of change in imaging biomarkers and clinical disease progression. Finally, we will determine the pathologic basis of the biomarker changes in DLB in autopsied patients, which is the gold standard for validating imaging biomarkers in Aim 4. In addition to these aims that focus on hypothesis testing, we will respond to RFA-NS- 16-022 by collecting whole blood, plasma, serum, CSF, and urine samples, clinical and harmonized neuroimaging data longitudinally; DNA and peripheral blood mononuclear cells from a prospective cohort of DLB patients, and submit them to the PDBP.