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

描述(申请人提供)：阿尔茨海默病、S病(AD)和抑郁症在 居家老年人，导致发病率增加，养老院安置和 死亡率比一般老年人口的死亡率要高。我们的横断面研究 波士顿地区已建立的居家人群发现低血浆淀粉样蛋白-A42 (Aa42)与抑郁症无关，与心血管疾病有关。我们进一步 发现低Aa42的抑郁症合并高Aa42的抑郁症与 记忆力不佳。同样，其他研究表明，高血浆AA40/AA42 比例显著增加AD的风险。多项研究表明，血浆AA 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 血浆中与抗体多肽相关的潜在抑郁亚型，我们称之为 淀粉样蛋白相关性抑郁症？此R01应用程序的目的是验证 由高血浆AA40/Aa42比率定义的淀粉样蛋白相关性抑郁症的存在，以及 调查此抑郁亚型是否是AD的前驱抑郁症。该提案是 基于我们现有的人口，有两个目标：目标1是记录记忆力下降 淀粉样蛋白相关性抑郁症患者与非淀粉样蛋白相关性抑郁症患者的前瞻性比较 抑郁VS对照。目的2探讨血浆AA与高血压的关系。 阿尔茨海默病的中枢神经系统标志物脑脊液AA在不同类型抑郁症中的作用 子组。我们的长期目标是识别AD的前驱症状，以帮助促进早期 在居家的老年人口中治疗这种疾病。 公共卫生相关性：这项拟议的纵向研究试图通过调查抑郁症和高血浆AA40/Aa42比率的组合是否会导致认知能力下降的风险更大，并在脑脊液中发现AD生物标志物，来验证淀粉样蛋白相关抑郁症是否与低血浆AA40/Aa42比率或没有抑郁症的人相比。

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.