Plasma and CSF Abeta peptides in late-onset major depression

描述（由申请人提供）：迟发性晚期生活重性抑郁症（迟发性LLMD）是一种具有病因和结果的异质性疾病。纵向和死后研究都发现，在第一次抑郁发作时认知完整的迟发性LLMD老年个体的一部分将在相对较短的随访期内发展为进行性认知衰退和/或临床和组织病理学诊断为阿尔茨海默病（AD）。阿尔茨海默病病理标准的形成需要几十年的时间，这意味着抑郁发作可能代表阿尔茨海默病的临床前或前驱期。然而，目前还没有生物标志物来识别那些患有前驱AD的晚发型LLMD患者。我们组和其他人在健康老年人中进行的研究结果表明，血浆淀粉样蛋白- β肽- ma (A/？A¿42/A/？在纵向随访期间，A¿42的比例和更大的下降与更大的认知能力下降和/或AD事件有关。我们的血浆A/? ?升高的横断面初步研究也有证据。老年LLMD患者的A/ 42和A$42/A¿40比值升高，脑脊液A/？42水平也曾在重度抑郁症患者中报道过。根据这些较早提出的调查结果，这项建议的主要目标是：(1)进行为期3年的纵向研究，验证老年迟发性LLMD患者在纵向随访期间血浆a /942水平和a #42/ a¿40比值高于对照组的假设；(2)检验a /042的测量是否与老年迟发性LLMD患者认知能力下降和/或AD的发生有关。另一个目标是确定血浆A/ff42水平的变化是否与脑脊液（CSF） A/ff42水平的类似变化平行。在一个学科的子集中有42个。如果这些假设得到证实，那么血浆A/？42可能成为一种容易获得的标志物，用于识别那些可能患有前驱AD的晚发型LLMD患者。

DESCRIPTION (provided by applicant): Late-onset late life major depression (late-onset LLMD) is a heterogeneous disorder with respect to etiology and outcome. Both longitudinal and post-mortem studies have found that a subset of elderly individuals with late-onset LLMD who are cognitively intact at the time of their first depressive episode will develop progressive cognitive decline and/or a clinical and histopathologic diagnosis of Alzheimer's disease (AD) within relatively brief follow-up periods. The many decades required for the pathologic AD criteria to develop implies that the depressive episode may represent a preclinical or prodromal phase of AD in a subset of individuals. However, there are presently no biological markers to identify those individuals with late-onset LLMD who have prodromal AD. Results from studies in healthy elderly conducted by our group and others suggest that higher baseline plasma amyloid beta peptide-Ma (A/?42) level, higher A¿42/A/?40 ratios and greater reductions in A¿42 during longitudinal follow-up, are associated with greater cognitive decline and/or incident AD. There is also evidence from our cross-sectional pilot study of elevated plasma A/?42 and A$42/A¿40 ratio in elderly individuals with LLMD, and elevated CSF A/?42 levels have also been reported previously in individuals with major depression. Based on these earlier suggestive findings, the major objectives of this proposal are: (1) to conduct a 3-year longitudinal study to test the hypothesis that elderly individuals with late-onset LLMD will have higher plasma A/942 level and A#42/A¿40 ratio and greater reductions in A¿42 during longitudinal follow-up relative to controls, and (2) to examine whether measures of A/042 will be associated with greater cognitive decline and/or the development of AD in elderly individuals with late-onset LLMD. Another goal is to determine if changes in plasma A/ff42 levels are paralleled by similar changes in cerebrospinal fluid (CSF) A/?42 in a subset of subjects. If these hypotheses are confirmed, then the determination of plasma A/?42 might become an easily obtainable marker to identify those individuals with late-onset LLMD who may have prodromal AD.