GERIATRIC DEMENTIA RESEARCH CLINIC

老年痴呆症研究诊所将专注于神经代谢方面 老年痴呆症在老年人中的发病率。葡萄糖氧化和 已知痴呆患者的大脑神经递质代谢降低 受试者在活体内。该计划项目是一组完整的 旨在阐明这些分子基础的研究 并测试它们在改善诊断方面的价值以及 它们潜在的病理生理和治疗意义。 来自痴呆症评估的精心诊断的患者和对照 临床和另一个尸检系列将被研究。新的信号分析方法 ~(133)Xenon洗脱曲线和胆碱能等的测量 将开发血液和脑脊液中的神经递质标记物 作为诊断的辅助。最近在本单元和两个单元中观察到的 英国实验室证实阿尔茨海默氏症存在内在异常 大脑中葡萄糖利用的两个关键酶--磷酸果糖激酶 (PFK)和丙酮酸脱氢酶(PDHC)。PFK、PDHC和其他组织的活动 来自生理相关的代谢和神经递质标志物酶 尸检阿尔茨海默病和对照大脑的区域将进行比较；PFK将 在非神经组织中也是如此，因为最近的数据表明 它的异常在阿尔茨海默氏症成纤维细胞中持续存在。在……里面 此外，PFK和PDHC的活性以及PFK的同工酶图谱将是 在临床患者的血细胞和成纤维细胞中进行了研究。这些 酶将从尸检组织中提纯并进行动力学和 用电泳法检测结构异常。铝，a 阿尔茨海默病中可能存在的神经毒素将被检测其影响 对兔脑内葡萄糖代谢的影响。有选择性的脆弱性 某些神经元对葡萄糖分解代谢受损的作用将在大鼠身上进行探索 以视网膜体外培养为模型系统。其他调查将研究 治疗剂、营养效应和可能的关系 免疫功能改变和内源性酶异常之间的关系 阿尔茨海默氏症淋巴细胞。这个关于阿尔茨海默氏症的神经化学的节目 疾病的另一个目的是寻找对它或对一种疾病有用的生化标记(S 对它的倾向性。

The Geriatric Dementia Research Clinic will focus on neurometabolic aspects of Alzheimer disease in the elderly. Glucose oxidation and neurotransmitter metabolism are known to decrease in the brains of demented subjects in vivo. This program project is an integrated group of investigations designed to elucidate the molecular bases of these abnormalities and to test their value in improving diagnoses, as well as their potential pathophysiologic and therapeutic significance. Meticulously diagnosed patients and controls from a Dementia Evaluation Clinic and another autopsy series will be studied. New signal analyses of 133Xenon washout curves and measurements of putative cholinergic and other neurotransmitter markers in blood and cerebrospinal fluid will be developed as aids to diagnosis. Recent observations in this unit and in two laboratories in England have demonstrated intrinsic abnormalities Alzheimer brainin two key enzymes of glucose utilization in--phosphofructokinase (PFK) and pyruvate dehydrogenase (PDHC). Activities of PFK, PDHC and other metabolic and neurotransmitter marker enzymes from physiologically relevant regions of autopsy Alzheimer and control brains will be compared; PFK will also be characterized in non-neural tissues, since recent data indicate that the abnormalities in it persist in Alzheimer fibroblasts. In addition, activities of PFK and PDHC and isozyme patterns of PFK will be studied in blood cells and fibroblasts from the clinic patients. These enzymes will be purified from autopsied tissues and studied kinetically and electrophoretically to test for structural abnormalities. Aluminum, a putative neurotoxin in Alzheimer disease, will be examined for its effects on glucose metabolism in rabbit brain. The selective vulnerability of certain neurones to impaired glucose catabolism will be explored with rat retina in vitro as a model system. Other investigations will study therapeutic agents, nutritional effects, and a possible relationship between altered immune function and intrinsic enzymatic abnormalities of Alzheimer lymphocytes. This program on the neurochemistry of Alzheimer's disease also aims to identify useful biochemical marker(s) for it or for a predisposition to it.