Morphologic/Neurochemical Correlates of Depression in AD

描述（由申请人提供）：重度抑郁症（MDD）是阿尔茨海默病（AD）的一种常见和重要的并发症，增加了患者及其家人的痛苦，产生过度残疾，促进机构化，并加速死亡。新出现的AD中MDD的临床病理学研究表明，AD的这种行为并发症的发展与脑干胺能核（SN、DR、LC）的变性和胆碱能bnM的相对保存相关。AD+MDD的这些神经病理学和相关神经化学相关性对于AD的这种行为并发症似乎是相对特异性的，并且可以解释在这种情况下MDD的病程和治疗反应性的方面。 我们建议使用125例经组织病理学确认的AID病例和对照来评估这一主要病因学假设，这些病例和对照由四个NIA资助的ADRC和老年精神病学分支、DIRP、NIMI-t组成的联盟进行了前瞻性特征描述。所有参与的研究中心都采用了痴呆症抑郁症临床评估（CADD），这是一种结构化的锚定诊断访谈，旨在可靠地诊断和表征这项正在进行的纵向研究中的重度抑郁发作（MDEs）。使用免疫染色的冷冻连续切片的严格体视学分析进行脑干核的神经变性的多维评估，并且通过建立的HPLC方法使用快速冷冻的组织样品进行确定的皮质和皮质下投射区域中的NT/代谢物的测定。 中学。假设探讨：a）临床亚型与这些神经病理学和神经化学变量的相关性，B）这些区域的细胞死亡机制，以及c）MDD家族史和APOE基因型对AD中MDD出现的影响。 拟议的研究计划的长期目标是更好地定义AD中的生物基质MDD，目的是增加知识基础，以促进更有效的治疗方法的开发，并为影响老年人的主要情绪障碍的临床生物学提供更多的见解。

DESCRIPTION (provided by applicant): Major Depressive Disorder (MDD) is a common and important complication of Alzheimer's disease (AD) that increases the suffering of patients and their families, produces excess disability, promotes institutionalization, and hastens death. Emerging clinicopathological studies of MDD in AD suggest that the development of this behavioral complication of AD is associated with degeneration of the brainstem aminergic nuclei (SN, DR, LC) and the relative preservation of the cholinergic bnM. These neuropathologic and related neurochemical correlates of AD+MDD appear to be relatively specific for this behavioral complication of AD, and may explain aspects of the course and treatment responsiveness of MDD in this context. We propose to evaluate this primary etiologic hypothesis using 125 histopathologically-confirmed AID cases and controls who were prospectively characterized by a consortium of four NIA-funded ADRCs and the Geriatric Psychiatry Branch, DIRP, NIMI-t. All participating sites employ the Clinical Assessment of Depression in Dementia (CADD), a structured, anchored diagnostic interview that was developed to reliably diagnose and characterize Major Depressive Episodes (MDEs) in this ongoing longitudinal study. Multidimensional assessments of neurodegeneration of the brainstem nuclei are performed using rigorous stereologic analyses of immunostained frozen serial sections, and determinatons of NTs/metabolites in defined cortical and subcortical projection areas are performed using flash-frozen tissue samples by established HPLC methods. Secondary. Hypotheses explore: a) the associations of clinical subtypes on these neuropathologic and neurochemical variables, b) the mechanism of cell death in these regions, and c) the influence of a family history of MDD and APOE genotype on the emergence of MDD in AD. The long-term goal of the proposed research plan is to better define the biological substrates MDD in AD, with the intention of augmenting the knowledge base that will facilitate the development of more effective treatments, and to provide additional insight into the clinical biology of Major Mood Disorders affecting the elderly.