Morphologic/Neurochemical Correlates of Depression in AD

描述(申请人提供)：严重抑郁障碍(MDD)是阿尔茨海默病(AD)的一种常见和重要的并发症，它增加了患者及其家人的痛苦，产生了过度的残疾，促进了制度化，并加速了死亡。阿尔茨海默病的临床病理研究表明，阿尔茨海默病的这种行为并发症的发生与脑干氨基核(SN、DR、LC)的变性和胆碱能BNM的相对保存有关。AD+MDD的这些神经病理和相关的神经化学相关性似乎对AD的这一行为并发症具有相对特异性，并可能在这一背景下解释MDD的病程和治疗反应的某些方面。 我们建议使用125例经组织病理学证实的AID病例和对照来评估这一主要病因学假说，这些病例和对照的特征是由NIA资助的四个ADRC和NIMI-T老年精神病学分支机构组成的联合体。所有参与网站都采用了痴呆症抑郁临床评估(CADD)，这是一种结构化的、支撑性的诊断访谈，旨在可靠地诊断和描述这项正在进行的纵向研究中的严重抑郁发作(MDE)。使用免疫染色连续切片的严格体视学分析对脑干核团的神经退行性变进行多维评估，并使用闪存冰冻组织样本按照建立的高效液相色谱方法测定确定的皮质和皮质下投影区的NTS/代谢物。 第二位。假说探索：a)临床亚型与这些神经病理和神经化学变量的关系，b)这些区域细胞死亡的机制，c)MDD家族史和APOE基因对AD中MDD发生的影响。 拟议研究计划的长远目标是更好地界定AD中MDD的生物底物，目的是增加知识基础，促进开发更有效的治疗方法，并对影响老年人的主要情绪障碍的临床生物学提供更多见解。

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.