Plasma Amyloid-beta Peptides, Depression and Alzheimer's Disease in the Homebound

血浆淀粉样β肽、居家中的抑郁症和阿尔茨海默病

• 批准号: 7883340
• 负责人: WEI QIAO Wendy QIU
• 金额: $ 40.67万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-15 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7883340
• 关键词: Alzheimer' s Disease; Alzheimer' s disease risk; Amyloid; Amyloid beta-Protein; Area; Biological Markers; Boston; Cardiovascular Diseases; Cerebrospinal Fluid; Cognition; Creatinine; Critiques; Cross-Sectional Studies; Disease; Early treatment; Education; Elderly; Equilibrium; Ethnic Origin; Gender; Goals; Impaired cognition; Language; Lead; Longitudinal Studies; Memory; Mental Depression; Morbidity - disease rate; Neuraxis; Neurobehavioral Manifestations; Neurology; Neuropsychology; Nursing Homes; Peptides; Plasma; Population; Risk; Staging; Stroke; Subgroup; base; mortality; public health relevance; research study; tau Proteins

DESCRIPTION (provided by applicant): Both Alzheimer?s disease (AD) and depression have become increasingly more prevalent in the homebound elderly, leading to increased rates of morbidity, nursing home placement and mortality, than what are found in the general elderly population. Our cross-sectional study of an established homebound population in the Boston area has found that low plasma amyloid-a42 (Aa42) is associated with depression independently of cardiovascular disease. We further found that depression with low Aa42 combined with high Aa42 in plasma is associated with poor memory. Similarly other research studies have shown that a high plasma Aa40/Aa42 ratio significantly increased the risk of AD. Multiple studies demonstrate that plasma Aa correlates with cerebral spinal fluid (CSF) Aa when cognition is normal, but this equilibrium disappears after the AD cognitive symptoms occur. We hypothesize the existence of a potential depression subtype associated with Ab peptides in plasma, which we have termed ?amyloid-associated depression?. The purpose of this R01 application is to validate the existence of amyloid-associated depression defined by a high plasma Aa40/Aa42 ratio, and to investigate whether this depression subtype is a prodromal depression of AD. The proposal is based on our established population, and has two aims: Aim 1 is to document memory decline prospectively in those with amyloid-associated depression vs. those with non-amyloid depression vs. the controls. Aim 2 is to investigate the relationship between plasma Aa and CSF Aa, a central nervous system (CNS) biomarker of AD, in the different depression subgroups. Our long-term goal is to identify prodromal signs of AD to help facilitate early treatment of the disease in the homebound elderly population. PUBLIC HEALTH RELEVANCE: The proposed longitudinal study seeks to validate amyloid associated depression by investigating whether the combination of depression and a high plasma Aa40/Aa42 ratio will lead to greater risk of cognitive decline and the finding of the AD biomarkers in CSF as compared to those with a low plasma Aa40/Aa42 ratio or those without depression.

描述（由申请人提供）：既阿尔茨海默氏症？AD和抑郁症在美国变得越来越普遍， 居家老年人，导致发病率、疗养院安置率和 死亡率，比一般老年人口。我们的横断面研究 波士顿地区的一个已建立的居家人群发现，低血浆淀粉样蛋白-a42 （Aa 42）与抑郁症相关，独立于心血管疾病。我们进一步 发现低Aa 42结合血浆中高Aa 42的抑郁症与以下相关： 记性不好。类似地，其他研究表明，高血浆Aa 40/Aa 42 比例显著增加AD的风险。多项研究表明， 当认知正常时，与脑脊液（CSF）Aa相关，但这种平衡 在AD认知症状出现后消失。我们假设存在一个 与血浆中的Ab肽相关的潜在抑郁亚型，我们称之为 ?淀粉样蛋白相关抑郁症？此R 01应用程序的目的是验证 存在淀粉样蛋白相关的抑郁症，定义为高血浆Aa 40/Aa 42比值，以及 研究这种抑郁亚型是否是AD的前驱抑郁。该提案 基于我们的既定人口，有两个目标：目标1是记录记忆衰退 在淀粉样蛋白相关抑郁症患者与非淀粉样蛋白相关抑郁症患者中， 抑郁症与对照组目的二是探讨血浆Aa与 AD的中枢神经系统（CNS）生物标志物CSF Aa在不同抑郁症中的表达 分组。我们的长期目标是识别AD的前驱症状，以帮助促进早期治疗。 治疗居家老年人的疾病。 公共卫生相关性：拟议的纵向研究旨在通过调查抑郁症和高血浆Aa 40/Aa 42比值的组合是否会导致认知能力下降的更大风险以及与低血浆Aa 40/Aa 42比值或无抑郁症的患者相比CSF中AD生物标志物的发现来验证淀粉样蛋白相关抑郁症。