Activity effects on Alzheimer neuropathology & dementia

活动对阿尔茨海默病神经病理学的影响

• 批准号: 6930496
• 负责人: MICHAEL P MCDONALD
• 金额: $ 29.6万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6930496
• 关键词: Alzheimer' s disease; amyloid proteins; body physical activity; brain; cell death; cognition; dementia; dietary supplements; folate deficiency; genetically modified animals; hippocampus; histology; homocysteine; laboratory mouse; memory disorders; mental disorder prevention; neuritic plaques; neuropathology

DESCRIPTION (provided by applicant): Epidemiological evidence suggests that ongoing mental or physical activity may attenuate the cognitive decline of Alzheimer's disease, or delay its onset. However, there are conflicting studies that do not show a benefit for increased cognitive activity or exercise for Alzheimer's patients. In addition, an alternate hypothesis suggests that some patients are predisposed to get Alzheimer's disease by early adulthood, and do not have the cognitive capacity or inclination to engage in mentally stimulating activity. The experiments proposed in this proposal are designed to establish cause-and-effect relationships between ongoing mental or physical activity and cognitive status in transgenic mice bearing the Swedish mutation of the amyloid precursor protein (APP). These transgenic mice develop Alzheimer-like amyloid plaques starting at approximately 10 months of age. When fed a folate-deficient diet supplemented with homocysteine for 3 months, APP transgenic mice, but not wild-type control mice, develop hippocampal-specific cell death. Thus we will be able to determine not only whether increased physical or mental activity improves cognitive performance but also whether it affects the rate of cell death or amyloid plaque formation, information that is not obtainable in human Alzheimer patients. Together, the data provided by the proposed experiments will inform us as to the potential effectiveness of cognitively stimulating activities or physical exercise as therapeutic or preventative measures in the fight against Alzheimer's disease.

描述（由申请人提供）：流行病学证据表明，持续的精神或身体活动可能减轻阿尔茨海默病的认知能力下降，或延缓其发病。然而，有相互矛盾的研究没有显示增加认知活动或锻炼对阿尔茨海默病患者有益。此外，另一种假设认为，一些患者在成年早期就容易患阿尔茨海默病，并且没有认知能力或倾向于从事精神刺激活动。本提案中提出的实验旨在建立携带淀粉样蛋白前体蛋白（APP）瑞典突变的转基因小鼠持续的精神或身体活动与认知状态之间的因果关系。这些转基因小鼠在大约10个月大的时候开始出现阿尔茨海默病样淀粉样斑块。在叶酸缺乏的饮食中添加同型半胱氨酸3个月后，APP转基因小鼠，而非野生型对照小鼠，出现海马特异性细胞死亡。因此，我们不仅能够确定增加的身体或精神活动是否能提高认知能力，而且还能确定它是否会影响细胞死亡或淀粉样斑块形成的速度，这些信息在人类阿尔茨海默病患者身上是无法获得的。总之，拟议实验提供的数据将告诉我们，作为治疗或预防阿尔茨海默病的措施，认知刺激活动或体育锻炼的潜在有效性。