Protein Molecular Imaging in Patients with Late-Life Major Depression

晚年重度抑郁症患者的蛋白质分子成像

• 批准号: 7389518
• 负责人: ANAND KUMAR
• 金额: $ 20.86万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7389518
• 关键词: Alzheimer' s Disease; Amyloid; Binding; Binding Proteins; Biochemical; Brain; Clinical; Cognition; Cognition Disorders; Cognitive; Communities; Dementia; Diagnosis; Disease; Early identification; Elderly; Goals; Hippocampus (Brain); Label; Lead; Literature; Longitudinal Studies; Major Depressive Disorder; Measures; Mental Depression; Moods; Neocortex; Neurobehavioral Manifestations; Neurobiology; Neurofibrillary Tangles; Outcome; Patients; Pattern; Performance; Positron-Emission Tomography; Prefrontal Cortex; Protein Binding; Proteins; Risk; Risk Factors; Sampling; Senile Plaques; Time; analog; base; executive function; geriatric depression; geriatric major depression; in vivo; interest; mild neurocognitive impairment; neuropathology; propylene; protein distribution; tau Proteins

DESCRIPTION (provided by applicant): The primary objective of this exploratory study is to examine the binding of protein molecules, both amyloid and tau, in the brain using positron emission tomography (PET) with fluorinated analog of 1, 1-dicyano-2-[6- (dimethylamino)-2-naphthalenyl] propene ([18F]FDDNP) in patients with late life major depression (MDD) and healthy controls. An additional goal is to examine the relationship of [18F]FDDNP binding, both globally and regionally, to specific measures of cognition (global cognition and measures of executive function and recall). Depression in late-life is both a risk factor and a prodrome for dementia, especially dementia of the Alzheimer Type (AD). FDDNP is a valid in vivo probe that binds to protein, both amyloid and tau (core biochemical components of neuritic plaques and neurofibrillary tangles in the brain respectively). FDDNP binding is higher in patients diagnosed with AD and mild cognitive impairment (MCI) when compared with control subjects and in vivo binding correlates well with post mortem evidence of neuropathology. Our proposal will help us cross- sectionally examine overall protein burden and its relationship to cognitive performance in patients with MDD. This preliminary project will lead to longitudinal studies that examine the relationship of FDDNP binding to long term clinical outcome and a comparison of binding patterns in MDD to patients diagnosed with probable AD. Our observations will have important implications for the neurobiology of mood and cognitive disorders in the elderly. 7. Project Narrative The study will help identify patients with late-life depression who may be 'at risk' for developing dementia of the Alzheimer Type over time. This will facilitate the early identification of patients who may benefit from aggressive therapy aimed at alleviating both mood and cognitive symptoms.

描述（由申请人提供）：这项探索性研究的主要目的是使用 1, 1-二氰基-2-氟化类似物的正电子发射断层扫描 (PET) 检查大脑中蛋白质分子（淀粉样蛋白和 tau 蛋白）的结合。 [6-（二甲氨基）-2-萘基]丙烯（[18F]FDDNP）用于晚年重度抑郁症（MDD）患者和健康对照。另一个目标是检查全球和区域范围内 [18F]FDDNP 结合与特定认知测量（整体认知以及执行功能和回忆的测量）的关系。晚年抑郁症既是痴呆症的危险因素，也是痴呆症的前驱症状，尤其是阿尔茨海默型痴呆症 (AD)。 FDDNP 是一种有效的体内探针，可与淀粉样蛋白和 tau 蛋白（分别是大脑中神经炎斑块和神经原纤维缠结的核心生化成分）结合。与对照受试者相比，诊断为 AD 和轻度认知障碍 (MCI) 的患者中 FDDNP 结合更高，并且体内结合与神经病理学的死后证据密切相关。我们的建议将帮助我们横断面检查 MDD 患者的总体蛋白质负荷及其与认知表现的关系。该初步项目将进行纵向研究，检查 FDDNP 结合与长期临床结果的关系，并将 MDD 中的结合模式与诊断为可能患有 AD 的患者进行比较。我们的观察将对老年人情绪和认知障碍的神经生物学产生重要影响。 7. 项目叙述 该研究将帮助识别患有晚年抑郁症的患者，随着时间的推移，这些患者可能有“风险”患上阿尔茨海默型痴呆。这将有助于及早识别可能受益于旨在缓解情绪和认知症状的积极治疗的患者。