Sex steroid hormones and risk of Alzheimer's Disease with age

随着年龄的增长，性类固醇激素和阿尔茨海默氏病的风险

• 批准号: 7055645
• 负责人: EMILY R ROSARIO
• 金额: $ 2.79万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-01 至 2008-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7055645
• 关键词: Alzheimer' s disease; aging; amyloid proteins; androgens; clinical research; dihydrotestosterone; disease /disorder proneness /risk; enzyme linked immunosorbent assay; gene expression; genetically modified animals; human tissue; immunocytochemistry; laboratory mouse; laboratory rat; male; molecular pathology; neuroendocrine system; neuroprotectants; predoctoral investigator; steroid hormone biosynthesis; tau proteins; testosterone; tissue /cell preparation; Alzheimer' s disease; aging; amyloid proteins; androgens; clinical research; dihydrotestosterone; disease /disorder proneness /risk; enzyme linked immunosorbent assay; gene expression; genetically modified animals; human tissue; immunocytochemistry; laboratory mouse; laboratory rat; male; molecular pathology; neuroendocrine system; neuroprotectants; predoctoral investigator; steroid hormone biosynthesis; tau proteins; testosterone; tissue /cell preparation

DESCRIPTION (provided by applicant): Advancing age is the most significant risk factor for the development of Alzheimer's disease (AD). Men, like women, experience a robust decline in circulating levels of their primary sex steroid hormones, testosterone (T) and its active metabolite dihydrotestosterone (DHT), as a consequence of normal aging. In men, decreases in testosterone leads to functional impairments in androgen-responsive tissues such as bone, muscle, heart, and brain that are often manifested as the clinical syndrome 'androgen deficiency in aging males'. As an androgen-responsive tissue, the brain may also be vulnerable to normal age-related reductions in T and DHT. Recent studies have shown that androgens are neuroprotective and regulate levels (?-amyloid (A?) protein. The goal of proposal is to determine if normal age-related androgen depletion will impair the beneficial actions of androgens, thereby increasing the vulnerability of the aging male brain to the development of AD pathology. The proposed studies will utilize a combination of animal models and analyses of human tissues to investigate the hypothesis that age-related androgen depletion increases the risk for developing AD.

描述（由申请人提供）：增长年龄是阿尔茨海默氏病（AD）发展的最重要的危险因素。男性像女性一样，其原发性类固醇激素，睾丸激素（T）及其活跃的代谢产物二氢睾丸激素（DHT）的循环水平下降，这是正常衰老的结果。在男性中，睾丸激素的减少会导致雄激素反应性组织（如骨，肌肉，心脏和大脑）的功能障碍，这些组织通常表现为临床综合征“雄性雄性雄激素缺乏”。作为雄激素反应性组织，大脑也可能容易受到T和DHT年龄相关的正常降低。最近的研究表明，雄激素是神经保护剂和调节水平（？ - 淀粉样蛋白（A？）蛋白。建议的目标是确定与年龄相关的正常雄激素消耗是否会损害雄激素的有益作用与年龄相关的雄激素耗竭增加了发展AD的风险。