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相关痴呆(ADRD)会出现神经精神症状(NPS)。这些令人衰弱的症状 包括抑郁、焦虑、冷漠、妄想、幻觉、烦躁、睡眠障碍 疾病进展更快，功能障碍更大，照顾者负担更重，更早 制度化。目前治疗MCI/痴呆的NPS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NPS。 然而，我们对NPS在MCI/痴呆中的分子机制的提名有限。 治疗靶点。为了解决这个知识鸿沟，我们的目标是阐明基因和分子 用两种互补但独立的方法研究MCI/痴呆中NPS的潜在机制。我们的 拟议的计划是使用串联的基于质量标记的蛋白质组学；然而，由于提交了 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经承诺 美国国立卫生研究院资助的许多新项目。这些新获奖项目的结果是减少了 核心，以在拟议的时间表内完成我们的拟议目标。这份增刊将支持及时 全脑蛋白质组学的吞吐量通过提议租赁拥有一个连接到一个 质谱计必须按照拟议的时间表完成拟议的具体目标。