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: 3768394
• 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/3768394
• 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.

阿尔茨海默病（AD）是人类主要的健康问题之一 老年人口。 记忆力进行性下降是其标志之一 该疾病的临床特征，以及给患者带来的痛苦 以及照顾者。 目前尚无有效治疗方法，且病因 仍然未知。 我们机构的初步工作已经取得了 鉴定缺陷的线粒体酶，细胞色素氧化酶 (CytOx)，存在于患有以下疾病的患者的小样本的血小板和脑组织中 广告。 CytOx 是线粒体电子传递中的一种复杂酶 正常神经元功能所必需的链，并且假设 这种缺陷可能代表一种特定于 广告。 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。 拟议的项目将 包括 100 名被诊断为可能患有 AD 的患者、50 名健康对照者， 以及50名帕金森病患者。 首先，灵敏度和 将评估 AD 中 CytOx 缺乏的特异性。 其次，我们将 检查痴呆程度和记忆障碍程度的关系 AD 组和对照组中的 CytOx 水平。 额外的分析将 重点关注每个细胞中 CytOx 和记忆功能的纵向变化 在两年的时间内对各组进行观察，以检查是否减少了 CytOx 值的变化与认知和认知的伴随变化相关。 记忆功能。 认知水平与认知水平之间存在密切关系 预计会出现记忆功能障碍和 CytOx 缺乏。 这些研究可能 除了增强我们的能力之外，还可以对 AD 进行有用的诊断测试 对记忆力下降疾病的认识，可能有进一步的了解 对未来潜在治疗途径的影响。