CYTOCHROME OXIDASE DEFICIENCY IN ALZHEIMER'S DISEASE

阿尔茨海默病中的细胞色素氧化酶缺乏

• 批准号: 3790412
• 负责人: CHRISTOPHER FILLEY
• 金额: --
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3790412
• 关键词: Alzheimer's disease; Parkinson's disease; aging; brain disorder diagnosis; cytochrome oxidase; dementia; diagnosis design /evaluation; disease /disorder classification; enzyme mechanism; human subject; longitudinal human study; neuropsychological tests; platelets

Alzheimer's disease (AD) represents one of the major health problems of the older population. Progressive memory decline is one of the hallmark clinical features of the disorder, and results in suffering for patients as well as caregivers. No effective treatment is available, and the etiology remains unknown. Preliminary work at our institution has resulted in the identification of a deficient mitochondrial enzyme, cytochrome oxidase (CytOx), in platelets and brain tissue of small samples of patients with AD. CytOx is a complex enzyme within the mitochondrial electron transport chain that is essential to normal neuronal function, and it is hypothesized that this deficiency may represent a biochemical lesion that is specific to AD. Whether this deficiency if fundamentally related to level of dementia and degree of memory disturbance is unknown. The proposed project will include 100 patients with a diagnosis of probable AD, 50 healthy controls, and 50 patients with Parkinson's disease. First, the sensitivity and specificity of CytOx deficiency in AD will be evaluated. Second, we will examine the degree of dementia and level of memory impairment in relation to CytOx levels in the AD and control groups. Additional analyses will focus on the longitudinal changes in CytOx and memory functioning in each of the groups over a two year period in order to examine whether decreases in CytOx values are associated with concomitant changes in cognitive and memory function. Strong relationships between level of cognitive and memory dysfunction and CytOx deficiency are expected. These studies may result in a useful diagnostic test for AD, in addition to enhancing our understanding of memory decline in the disease, and may have further implications for potential treatment avenues in the future.

阿尔茨海默氏病（AD）是老年人的主要健康问题之一， 老年人口。 记忆力的逐渐衰退 疾病的临床特征，并导致患者的痛苦， 以及护理人员。 没有有效的治疗方法，病因是 仍然未知。 在我们机构的初步工作已经导致了 一种缺陷型线粒体酶细胞色素氧化酶鉴定 （CytOx），在血小板和脑组织的小样本的患者， AD. CytOx是线粒体电子传递中的复杂酶 链是必不可少的正常神经元功能，它是假设 这种缺陷可能代表了一种生物化学病变， AD. 这种缺陷是否与痴呆程度有根本关系 记忆障碍的程度尚不清楚 拟议项目将 包括100名诊断为可能AD患者，50名健康对照， 和50名帕金森病患者。 首先，灵敏度和 将评价AD中CytOx缺乏的特异性。 二是 检查痴呆的程度和记忆障碍的程度， 与AD组和对照组中的CytOx水平。 其他分析将 关注细胞色素氧化酶和记忆功能的纵向变化， 两年后，为了检查是否减少， CytOx值与认知和 记忆功能 认知水平与 记忆功能障碍和CytOx缺乏。 这些研究可能 结果是一个有用的诊断测试AD，除了提高我们的 了解记忆力下降的疾病，并可能有进一步的 对未来潜在治疗途径的影响。