Investigating the role of ApoE4 and amyloid beta in susceptibility to neurologic complications after brain radiotherapy

摘要 阿尔茨海默病(AD)和相关的神经退行性疾病是进行性认知的常见原因 随着年龄的增长而下降。影响阿尔茨海默病风险的基因变异很普遍，可能是一种 生物标记物，并使开发AD特异性方法在上下文中保护神经功能成为可能 其他与年龄相关的疾病，其共病和治疗可能会加剧神经恶化 这发生在公元后。在老年人中，癌症是一种重要而常见的并存疾病。使用AD的模型， 这项建议研究了接受癌症指导治疗后可能发展成的神经认知功能障碍。 对大脑来说，其机制目前还知之甚少。这份提案调查了 与神经退行性疾病相关的遗传因素使个体在术后易患神经认知功能减退 脑部放射治疗。这项工作的结果将确定致病因素之间的基本关系 癌症治疗后潜在的AD和神经功能的过程，然后可能被用来发展 尽量减少阿尔茨海默病患者或有阿尔茨海默病风险的患者的治疗导致的神经认知缺陷的策略。

Abstract Alzheimer’s disease (AD) and related neurodegenerative disorders are common causes of progressive cognitive decline with age. Genetic variants that influence the risk of developing AD are prevalent and could serve as a biomarker and enable the development of AD-specific approaches that protect neurologic function in the context of other age-related diseases whose co-morbidities and therapies may compound the neurologic deterioration that occurs in AD. An important and common co-morbidity in aging individuals is cancer. Using models of AD, this proposal examines the neurocognitive dysfunction that can develop after receiving cancer therapies directed to the brain, the mechanisms of which are currently poorly understood. This proposal investigates whether genetic factors associated with neurodegenerative disease predispose individuals to neurocognitive decline after brain radiation therapy. The results of this work will identify fundamental relationships between pathogenic processes underlying AD and neurologic function after cancer therapy that may then be used to develop strategies that minimize therapy-induced neurocognitive deficits in individuals with AD or at risk for AD.