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）是一种病因和结局异质性疾病。纵向和尸检研究都发现，在第一次抑郁发作时认知完整的迟发性LLMD老年人的子集将在相对较短的随访期内发展为进行性认知下降和/或阿尔茨海默病（AD）的临床和组织病理学诊断。病理性AD标准的发展需要数十年的时间，这意味着抑郁发作可能代表了一部分个体中AD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的迟发性LLMD个体。我们小组和其他人在健康老年人中进行的研究结果表明，较高的基线血浆淀粉样β肽-Ma（A/？42)水平，更高的A <$42/A/？在纵向随访期间，A40比值和A42的较大降低与较大的认知下降和/或AD事件相关。也有证据表明，从我们的横断面试点研究血浆A/？42和A $42/A <$40比值，并升高CSF A/？42水平也曾在重度抑郁症患者中报道过。基于这些早期的提示性发现，本提案的主要目的是：（1）进行一项为期3年的纵向研究，以验证晚发LLMD的老年人血浆A/942水平和A#42/A#40比值较高以及A#42/A#40比值较低的假设。在纵向随访期间相对于对照组，以及（2）检查A/042的测量是否与患有晚发型LLMD的老年个体中更大的认知下降和/或AD的发展相关。另一个目标是确定血浆A/ff 42水平的变化是否与脑脊液（CSF）A/ff 42水平的变化相似。42例受试者。如果这些假设得到证实，那么血浆A/？42可能成为一个容易获得的标志物，以确定那些晚发型LLMD的人可能有前驱AD。

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.