DNA REPAIR IN AUTOPSY-PROVEN ALZHEIMER'S DISEASE

越来越多的证据表明，在非神经元细胞中存在DNA修复缺陷， 阿兹海默症的病人 有人提出了一种假设，即这种缺陷 可能与老年痴呆症的病因密切相关。 之一 许多旨在发现活细胞的研究的局限性 阿尔茨海默病的病因是缺乏足够数量的 非神经元细胞系可从病理学证实的阿尔茨海默氏病中获得 疾病病例。 本研究将通过调查来规避这个问题 在尸检时从患有以下疾病的患者中收集的皮肤成纤维细胞 神经病理学研究 这项研究将确定分布 5种不同形式的损伤的DNA修复效率 不同的试剂（甲磺酸甲酯、X射线、紫外线 光，丝裂霉素C和甲醛）在3个年龄匹配的人群中， 大约50名患者，即尸检证实的阿尔茨海默病， 尸检证实的非阿尔茨海默病脑疾病（疾病对照）和 尸检证实的正常大脑（正常对照）。 的技术 将使用程序外DNA合成和DNA的碱洗脱大小测定。 这项研究将明确定义DNA修复缺陷之间的关系 和老年痴呆症 它将证明DNA修复效率 是神经元变性的潜在原因，以及它是否可以 被用作阿尔茨海默病的实验室诊断工具。 本研究 还将提供30个经尸检证实的阿尔茨海默病成纤维细胞系， 到NIA细胞库，卡姆登，新泽西，供整个 科学界。

Evidence is accumulating of a DNA repair defect in non-neuronal cells of Alz-heimer's patients. The hypothesis has been advanced that this defect might be closely related to the cause of Alzheimer's disease. One of the limitations of many investigations of living cells aimed at discovering the etiology of Alzheimer's disease is the lack of a sufficient number of non-neuronal cell lines available from pathologically-confirmed Alzheimer's disease cases. This study will circumvent this problem by investigating skin fibroblasts collected at autopsy from patients having neuropathological investigations. This study will define the distribution of DNA repair efficiency for 5 different forms of damage produced by 5 different agents (methyl methane sulfonate, x-irradiation, ultraviolet light, mitomycin C and formaldehyde) in 3 age-matched populations, each of about 50 patients, namely autopsy-proven Alzheimer's disease, autopsy-proven non-Alzheimer brain disease (disease controls) and autopsy-proven normal brains (normal controls). The techniques of unscheduled DNA synthesis and alkaline elution sizing of DNA will be used. This study will clearly define the relationship between DNA repair defects and Alzheimer's disease. It will demonstrate whether DNA repair efficiency is a potential cause of the neuronal degeneration, and whether it can be used as a laboratory diagnostic tool for Alzheimer's disease. This study will also provide 30 autopsy-confirmed Alzheimer's disease fibroblast lines to the NIA Cell Repository, Camden, New Jersey, for use by the whole scientific community.