Longitudinal Imaging Biomarkers of Disease Progression in DLB

项目总结/摘要 路易体痴呆（Dementia with Lewy bodies，DLB）是一种以路易体为特征的临床综合征 阿尔茨海默病（AD）是一种常见的阿尔茨海默病（LBD），但其他阿尔茨海默病（AD）相关的病理学也常见于患有LBD的患者中。 DLB。尽管这两种病理中的每一种对临床疾病进展的影响并不完全清楚， 据了解，许多DLB患者可能受益于针对AD和LBD相关的治疗。 病理过程。为了准备DLB的这些临床试验，我们需要强大而可靠的生物标志物 可以跟踪疾病进展，特别是LBD和AD相关病理的进展。 我们提出了多模态成像生物标志物的病理过程中常见的患者， DLB检测疾病进展。我们建议建立一个DLB患者的纵向队列， 采集临床和多模态成像生物标志物数据以对纵向成像生物标志物进行建模 DLB中临床疾病进展方面的变化。在目标1中，我们建议确定是否 SPECT上LBD相关的多巴胺能损失，以及用高淀粉样蛋白-β测量的AD病理生理学 PET上的沉积和MRI上的AD特征萎缩与临床疾病的发生率相关 在目标2中，我们将确定这些纵向研究结果是否与DLB的进展、认知功能下降和生存率相关。 成像生物标志物和临床结果的变化，及其相关性受到遗传、性别的影响， 基础，与脑血管疾病相关的功能。在目标3中，我们将确定tau配体的模式 与对照相比，DLB中的AV-1451摄取及其与成像变化率的关系 生物标志物和临床疾病进展。最后，我们将确定的病理基础， 尸检患者中DLB的生物标志物变化，这是验证成像的金标准 目标4中的生物标志物。除了这些目标，重点是假设检验，我们将回应RFA-NS- 16-022通过采集全血、血浆、血清、CSF和尿液样本，临床和协调 神经影像学数据纵向; DNA和外周血单核细胞从一个前瞻性队列， DLB患者，并提交给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.