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），阿尔茨海默氏病（AD）或 AD相关的痴呆症（ADRD）经历神经精神症状（NPS）。这些使人衰弱的症状 包括抑郁症，焦虑，冷漠，妄想，幻觉，躁动，睡眠障碍，并相关 随着疾病进展的速度，功能障碍更大，护理人员负担更高，并且更早 制度化。 MCI/痴呆症中NP的当前治疗方法有限，但不良率很高 副作用，包括更高的死亡率。因此，迫切需要对NP的安全有效治疗。 但是，我们对MCI/痴呆中NP的分子机制的见解有限 治疗靶标。为了解决这一知识差距，我们旨在阐明遗传和分子 使用两种互补但独立的方法，MCI/痴呆症中NP的机制。我们的 拟议的计划是使用串联质量标记的蛋白质组学；但是，自从提交 提案和授予资金，Emory Core蛋白质组学设施的设备现已提交 许多新的NIH资助项目。这些新授予的项目的后果是降低的能力 完成我们提出的目标的核心目标是拟议的时间表。该补充将支持及时 通过提议将液态色谱租用到A 质谱仪完成提出的时间表之后提出的特定目的。