AMYLOID BETA PROTEIN IN CSF AND FAMILIAL AGGREGATION IN ALZHEIMER'S DISEASE

脑脊液中的β淀粉样蛋白和阿尔茨海默病的家族聚集

• 批准号: 6267311
• 负责人: KENNETH L DAVIS
• 金额: $ 14.51万
• 依托单位: MOUNT SINAI SCHOOL OF MEDICINE OF CUNY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-04-15 至 1999-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6267311
• 关键词: Alzheimer's disease; amyloid proteins; cerebrospinal fluid; disease /disorder proneness /risk; family genetics; human morbidity; human subject; interview; mathematical model; mental health epidemiology; nervous system disorder epidemiology; peptides; protein sequence; questionnaires

The presence of Abeta in CSF has a number of exciting implications for understanding Alzheimer's disease. Although data already gathered makes it highly unlikely that Abeta in CSF will be a diagnostic test for Alzheimer's disease, it may nonetheless, be useful in elucidating some of the heterogeneity that exists in the disease. Specifically, one goal of this study is to determine whether Alzheimer's disease probands with higher concentrations of Abeta have first degree relatives with a different morbid risk for Alzheimer's disease than the first degree relatives or probands with a lower concentration of Abeta, or alternatively, whether the age of onset of progressive dementia in first degree relatives can be differentiated by CSF Abeta concentrations. To achieve these goals, CSF will be obtained from Alzheimer's patients in whom the first degree relatives will be evaluated through the family history method to determine the incidence of Alzheimer's disease and related dementias, and age of onset. CSF Abeta will be measured in the laboratory of Steven Younkin at Case Western Reserve. Dr. Younkin's current antibody identifies the 40,41,42 and 43 amino acid sequences of Abeta peptides. However, work at Case Western Reserve will be directed toward developing a specific antibody that can differentiate the 40 vs. 41 and 42 amino acid sequences to determine if either sequence is more revealing than measurements of the combined 4kDa proteins.

CSF中Abeta的存在对以下方面具有许多令人兴奋的意义： 了解老年痴呆症 尽管已经收集的数据表明， CSF中Abeta极不可能成为阿尔茨海默氏症的诊断测试 疾病，尽管如此，它可能有助于阐明一些 疾病中存在的异质性。 具体来说， 这项研究是为了确定阿尔茨海默病的先证者是否具有更高的 Abeta的浓度有一级亲属与不同的病态 阿尔茨海默病的风险比一级亲属或先证者高 与较低浓度的Abeta，或者，无论年龄 一级亲属中进行性痴呆的发病可能是 通过CSF Abeta浓度区分。 为了实现这些目标，CSF 将从老年痴呆症患者中获得， 亲属将通过家族史方法进行评估，以确定 老年痴呆症和相关痴呆症的发病率， 发病 CSF Abeta将在Case的Steven Younkin实验室进行测量 西部保留地。 扬金博士目前的抗体识别出了404142 和Abeta肽的43个氨基酸序列。 但是，在Case 西储将致力于开发一种特异性抗体， 可以区分40与41和42个氨基酸序列，以确定 这两个序列中的任何一个都比4kDa的组合测量更能揭示问题， proteins.