MONOAMINES IN ALZHEIMER'S DISEASE/COULOMETRIC DETECTION

尽管我们对阿尔茨海默型痴呆症的认识有了新的进展， (DAT)其病因仍不清楚。 目前尚不清楚是否胆碱能 在大多数DAT患者中检测到的缺陷是主要的病理过程 或其他过程的结果。 有相当多的证据 表明除乙酰胆碱外的神经递质也参与其中 DAT。 我们已经发现了一个强有力的证据表明多巴胺能神经元参与 和肾上腺素能系统，并希望继续这项调查。 这项工作将包括应用一种新的方法，电化学 检测脑脊液（CSF）中的物质。 该检测 包括使用多个库仑电极 电压。 我们有初步证据表明 使用安培检测的色谱法导致错误的高 DOPAC、HVA、MHPG、5-HT和5-HIAA的CSF浓度估计值。 这 误差是由于存在共洗脱干扰化合物， 用安培法无法区分，但可与 使用库仑门检测真实的单胺代谢物， 多个传感器 另外库仑法更灵敏 并且允许检测去甲肾上腺素， 肾上腺素和多巴胺 6传感器系统库仑系统的调查也表明， 5-HTP和5-HT以已经氧化的形式存在 的5-羟基基团，大概醌。 部分氧化的 DAT CSF中的5-HT（5-HT-e）不被单胺氧化酶代谢。 这 这可能解释了5-HT和5-HIAA水平的异常关系。 我们以前发现的DAT CSF的吻部部分。 有可能 5-HT-e-参与DAT的发病机制，因为5-HT-e-具有神经毒性作用。 6-羟基-多巴胺通过醌中间体的形成介导。 在这个项目中，我们将研究单胺及其代谢产物，如 以及5-HT和其他干扰物质的异常形式，使用 多检测器库仑系统的高级版本。 我们计划 研究这些化合物并比较它们在对照和DAT的CSF中的含量 患者 存在单胺浓度的特定变化，或 特异性干扰化合物不仅可以提供诊断， 但它也会给我们一个线索的发病机制 DAT。 5-HT-e-在DAT中的可能作用将通过测量 DAT脑中的5-HT-e-和5-HT-e-神经毒性研究。

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.