MONOAMINES IN ALZHEIMER'S DISEASE/COULOMETRIC DETECTION

尽管我们对阿尔茨海默型痴呆的理解最近取得了进展 (DAT)其病因尚不清楚。目前尚不清楚胆碱能 在大多数DAT患者中检测到的缺陷是主要的病理过程 或者是其他过程的结果。有相当多的证据 提示乙酰胆碱以外的神经递质参与了 达特。我们发现了一个强有力的证据表明多巴胺能 和5-羟色胺能系统，并希望继续这项研究。 这项工作将包括一种新的电化学方法的应用 脑脊液中物质的检测。这项检测 涉及多个库仑电极的使用，这些电极设置在不同的位置 电压。我们有初步证据表明液体 使用安培检测的层析导致错误的高 脑脊液中DOPAC、HVA、MHPG、5-羟色胺和5-HIAA浓度的估计。这 误差是由于共洗脱干扰化合物的存在 不能用安培法区分，但可以与 用库仑门和库仑法测定单胺类代谢物 多个传感器。除了库仑法外，库仑法更灵敏 而不是安培法，可以检测去甲肾上腺素， 脑脊液中的肾上腺素和多巴胺。 对6传感器系统的库仑测量系统的研究也表明 以已经氧化的形式存在的5-羟色胺和5-羟色胺 5-羟基团，推测为对苯二酚。部分氧化的 DAT脑脊液中的5-羟色胺(5-HT-e)不被单胺氧化酶代谢。这 可以解释5-羟色胺和5-HIAA水平的异常关系 我们以前发现的DAT脑脊液的吻部部分。有可能是 5-羟色胺-e-参与DAT的发病机制 6-羟基多巴胺是由苯二酮中间体的形成所介导的。 在这个项目中，我们将研究单胺及其代谢物，如 以及异常形式的5-羟色胺和其他干扰物质，使用 先进版本的多探测器库仑测量系统。我们计划 研究这些化合物，并比较对照组和DAT患者脑脊液中的这些化合物 病人。存在单胺浓度的特定变化或 一种特定的干扰化合物不仅可以提供诊断 DAT的程序，但它也将为我们提供发病机制的线索 达特。5-羟色胺-e-在DAT中的可能作用将通过测量来测试 DAT脑内5-羟色胺-e-和5-羟色胺-e-神经毒性的研究。

Despite recent advances in our understanding of dementia of Alzheimer type (DAT) its etiology is still unknown. It is not known if the cholinergic deficit, detected in most DAT patients, is the primary pathological process or a consequence of other processes. There is considerable evidence indicating involvement of neurotransmitters other than acetylcholine in DAT. We have found a strong evidence for involvement of the dopaminergic and serotoninergic systems and would like to continue this investigation. This work will include application of a new approach to electrochemical detection of substances in cerebrospinal fluid (CSF). This detection involves use of multiple coulometric electrodes which are set at different voltages. We have a preliminary evidence indicating that liquid chromatography using amperometric detection leads to erroneously high estimates of CSF concentrations of DOPAC, HVA, MHPG, 5-HT and 5-HIAA. This error is due to presence of co-eluting interfering compounds which are indistinguishable by the amperometric method but can be differentiated from the authentic monoamine metabolites by the use of coulometric gates and multiple sensors. In addition to the coulometric method is more sensitive than the amperometric one and allows detection of norepinephrine, epinephrine and dopamine in CSF. Investigation with a 6-sensor system coulometric system also indicated presence of 5-HTP and 5-HT in a form which had already undergone oxidation of the 5-hydroxy group, presumably to the quinone. The partially oxidized 5-HT (5-HT-e) in DAT CSF is not metabolized by monomine oxidase. This could explain the aberrant relationship of 5-HT and 5-HIAA levels in rostral fraction of DAT CSF found by us previously. It is possible that 5-HT-e- participates in pathogenesis of DAT, since the neurotoxic effect of 6-hydroxy-dopamine is mediated by formation of a quinone intermediate. In this project we will investigate monoamines and their metabolites, as well as the abnormal form of 5-HT and other interfering substances, using an advanced version of the multidetector coulometric system. We plan to investigate these compounds and compare them in CSF from controls and DAT patients. The presence of a specific change of monoamine concentration or a specific interfering compound would provide not only a diagnostic procedure for DAT but it would give us also a clue for the pathogenesis of DAT. The possible role of 5-HT-e- in DAT will be tested by measuring 5-HT-e- in DAT brains and by investigation of 5-HT-e-neurotoxicity.