Plasma and CSF Abeta peptides in late-onset major depression

描述(由申请人提供)：晚发性老年重度抑郁症(晚发性LLMD)是一种病因和预后方面的异质性疾病。纵向和尸检研究都发现，晚发性LLMD的一部分老年人在第一次抑郁发作时认知功能完好无损，他们将在相对较短的随访期内发展为进行性认知衰退和/或阿尔茨海默病(AD)的临床和组织病理学诊断。病理性AD标准的制定需要几十年的时间，这意味着抑郁发作可能代表了一部分人的AD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的晚发性LLMD患者。我们小组和其他人在健康老年人中进行的研究结果表明，基线血浆淀粉样β多肽-mA(A/？42)水平较高，A？42/A/？40比值较高，A？42在纵向随访期间下降较多，与认知功能下降和/或AD的发生有关。我们的横断面初步研究也有证据表明，患有LLMD的老年患者血浆A/？42和A$/A？40比值升高，严重抑郁症患者的脑脊液A/？42水平也升高。基于这些早期的提示性发现，这项建议的主要目标是：(1)进行一项为期3年的纵向研究，以检验以下假设：与对照组相比，晚发性LLMD老年患者的血浆A/942水平和A#42/A？40比率更高，而A#42/A？42的水平更大；(2)研究A/042的测量是否与迟发性LLMD老年个体的认知功能下降和/或AD的发展有关。另一个目标是确定在一组受试者中，血浆A/FF42水平的变化是否与脑脊液(CSF)A/？42的类似变化平行。如果这些假设得到证实，那么血浆A/？42的测定可能成为一种容易获得的标记物，用来识别那些可能患有前驱AD的晚发性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.