MORPHOLOGIC/NEUROCHEMICAL CORRELATES OF DEPRESSION IN AD

虽然阿尔茨海默病是典型的全球性和渐进性 认知能力下降，出现临床显著的行为 综合征在这种疾病中也很常见（Wragg和Jeste，1989）。 重度抑郁症患者的患病率估计 阿尔茨海默病的发病率从0%到86%不等， 范围为20%至25%。 然而，神经病理学和神经化学 这一重要的并发症来源的相关因素尚未被 系统地研究。 先前的临床、药理学和生化证据支持 几种神经递质系统在主要脑梗死发病机制中的作用 萧条 在本申请中，我们建议审查 阿尔茨海默病背景下重性抑郁症的形态学相关性 疾病的重点是三个胺能核，蓝斑， 黑质和中缝背核，以及各自的 神经递质/代谢物水平在这些核的投射区。 作为胆碱能功能障碍的指标， 乙酰转移酶特异性活性与抑郁症的发生 也将被确定。 假设：AD背景下的重度抑郁症与（1） 蓝斑，黑质， 和中缝背核;（2）在各自的减少 单胺能神经递质去甲肾上腺素，多巴胺和血清素， 这些核团的投射区域;和（3）相对保存 这些核团投射到的大脑区域中的ChAT活动。 作为 辅助具体目标，我们还将测试假设，一个家庭， 一级亲属中有重度抑郁症病史是一种风险 AD先证者出现重性抑郁的因素。

Although Alzheimer's disease is typified by global and progressive cognitive decline, the emergence of clinically-significant behavioral syndromes is also common in this disorder (Wragg and Jeste, 1989). Estimates of the prevalence of major depression among patients with Alzheimer's disease has ranged from 0% to 86%, with most estimates in the range of 20% to 25%. Yet, the neuropathological and neurochemical correlates of this important source of comorbidity have not been systematically studied. Previous clinical, pharmacologic, and biochemical evidence have supported a role for several neurotransmitter systems in the pathogenesis of major depression. In the current application, we propose to examine the morphological correlates of major depression in the context of Alzheimer's disease by focusing on three aminergic nuclei, the locus ceruleus, the substantia nigra, and the dorsal raphe nuclei, as well as the respective neurotransmitter/metabolite levels in the projection areas of these nuclei. As an index of cholinergic dysfunction, the relationship of choline acetyltransferase-specific activity to the emergence of major depression will also be determined. Hypotheses: Major depression in the context of AD is associated with (1) increased cytopathologic features in the locus ceruleus, substantia nigra, and the dorsal raphe nucleus; (2) a reduction in the respective monoaminergic neurotransmitters norepinephrine, dopamine, and serotonin in the projection areas of these nuclei; and (3) the relative preservation of ChAT activity in the brain regions to which these nuclei project. As an ancillary specific aim, we will also test the hypothesis that a family history of major depressive disorder among first-degree relatives is a risk factor for the emergence of major depression in probands with AD.