MORPHOLOGIC/NEUROCHEMICAL CORRELATES OF DEPRESSION IN AD

尽管阿尔茨海默氏症的特点是全球性和进行性 认知能力下降，出现临床上有意义的行为 综合征在这种疾病中也很常见(Wrag和Just，1989)。 对慢性阻塞性肺疾病患者中重度抑郁症患病率的估计 阿尔茨海默氏症的发病率从0%到86%不等，大多数估计在 20%到25%的范围。然而，神经病理和神经化学 这一共病的重要来源的相关性尚未得到 对其进行了系统研究。 先前的临床、药理学和生化证据都支持 几种神经递质系统在重症肌无力发病机制中的作用 抑郁症。在当前的应用程序中，我们建议检查 阿尔茨海默病背景下抑郁症的形态相关性 疾病通过集中在三个胺能核，蓝斑， 黑质和中缝背核，以及各自的 这些核团投射区域的神经递质/代谢物水平。 作为胆碱能功能障碍的一个指标，胆碱与 乙酰转移酶特异性活性与抑郁症的发生 也将被确定。 假设：阿尔茨海默病背景下的重度抑郁与(1) 蓝斑、黑质、 和中缝背核；(2)各自的 单胺能神经递质去甲肾上腺素、多巴胺和5-羟色胺 这些核的投射面积；以及(3)这些核的相对保存 这些核团投射到的大脑区域中的ChAT活动。作为一种 附带的特定目标，我们还将检验一个家庭的假设 一级亲属中有严重抑郁障碍史是一种风险 阿尔茨海默病先证者出现重度抑郁的因素。

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.