A brain multi-omic approach to identify key molecular drivers of neuropsychiatric

识别神经精神关键分子驱动因素的大脑多组学方法

• 批准号: 10649953
• 负责人: Aliza Pham Wingo
• 金额: $ 22.69万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-01 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10649953
• 关键词: Address; Agitation; Alzheimer' s Disease; Alzheimer' s disease patient; Alzheimer' s disease related dementia; Anxiety; Award; Brain; Caregiver Burden; Coupled; Delusions; Dementia; Disease Progression; Equipment; Funding; Genetic; Hallucinations; Individual; Institutionalization; Knowledge; Liquid Chromatography; Mental Depression; Molecular; Participant; Proteomics; Sampling; Sleep disturbances; Time; TimeLine; United States National Institutes of Health; base; disabling symptom; effective therapy; experience; functional disability; insight; mass spectrometer; mild cognitive impairment; mortality; multiple omics; neuropsychiatric symptom; neuropsychiatry; side effect; therapeutic target

Approximately 65% of individuals with mild cognitive impairment (MCI), Alzheimer's disease (AD), or AD related dementias (ADRD) experience neuropsychiatric symptoms (NPS). These debilitating symptoms include depression, anxiety, apathy, delusions, hallucinations, agitation, sleep disturbances and are associated with faster disease progression, greater functional impairment, higher caregiver burden, and earlier institutionalization. Current treatments for NPS in MCI/dementia have limited efficacy but high rates of adverse side effects, including higher mortality. Therefore, safe and effective treatments for NPS are urgently needed. However, we have limited insights into molecular mechanisms of NPS in MCI/dementia to nominate therapeutic targets. To address this knowledge gap, we aim to elucidate the genetic and molecular mechanisms underlying NPS in MCI/dementia using two complementary but independent approaches. Our proposed plan was to use tandem mass tagged-based proteomics; however, since the submission of the proposal and the awarding of funding, the equipment at the Emory Core Proteomics facility is now committed to many new NIH-funded projects. The consequence of these newly awarded projects is reduced capacity of the Core to complete our proposed aims at the proposed timeline. This supplement will support the timely throughput of the whole brain proteomics by proposing to lease-to-own a liquid chromatography coupled to a mass spectrometer to complete the proposed specific aims following the proposed timeline.

大约65%的轻度认知障碍（MCI）、阿尔茨海默病（AD）或 AD相关性痴呆（ADRD）经历神经精神症状（CNS）。这些衰弱的症状 包括抑郁、焦虑、冷漠、妄想、幻觉、激动、睡眠障碍，并与 疾病进展更快，功能障碍更严重，护理人员负担更重， 制度化。目前治疗MCI/痴呆的药物疗效有限，但不良反应发生率高。 副作用，包括更高的死亡率。因此，迫切需要安全有效的治疗方法。 然而，我们对MCI/痴呆患者中BMPs的分子机制的了解有限， 治疗目标为了解决这一知识缺口，我们的目标是阐明遗传和分子 使用两种互补但独立的方法研究MCI/痴呆的潜在机制。我们 拟议的计划是使用串联质量标记为基础的蛋白质组学;然而，由于提交的 根据提案和资金的授予，埃默里核心蛋白质组学设施的设备现在已投入使用 许多新的NIH资助项目。这些新授予的项目的后果是降低了 核心在提议的时间轴完成我们提议的目标。这一补充将及时支持 全脑蛋白质组学的吞吐量，通过建议租赁到自己的液相色谱耦合到 质谱仪按照拟定的时间轴完成拟定的具体目标。