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

研究 ApoE4 和 β 淀粉样蛋白在脑放疗后神经系统并发症易感性中的作用

基本信息

批准号：
10288163
负责人：
Jean Nakamura
金额：
$ 46.68万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-30 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10288163
关键词：
Adult Aftercare Age Aging Alzheimer&apos s Disease Alzheimer&apos s disease brain Alzheimer&apos s disease diagnosis Alzheimer&apos s disease model Alzheimer&apos s disease patient Alzheimer&apos s disease risk Amyloid beta-Protein Amyloid beta-Protein Precursor Anatomy Biological Biological Markers Brain Brain Injuries Cancerous Clinic Clinical Treatment Cranial Irradiation Custom DNA Damage DNA Double Strand Break DNA Markers Dementia Deposition Deterioration Development Diagnosis Disease Dose Dose Fractionation Elderly Functional disorder Genes Genetic Genotype Goals Guidelines Health Human Amyloid Precursor Protein Image Impaired cognition In Situ Individual Injury Learning Life Malignant Neoplasms Malignant neoplasm of brain Mediating Memory Modeling Molecular Mus Mutation Nerve Degeneration Nervous System Physiology Neurocognitive Neurocognitive Deficit Neurodegenerative Disorders Neurologic Neuronal Injury Neurons Normal tissue morphology Pathogenicity Patients Performance Population Predisposition Process Progressive Disease Proteins Radiation Radiation Dose Unit Radiation therapy Risk Risk Assessment Risk Estimate Risk Factors Role Structure Techniques Therapeutic Tissues Toxic effect Transgenic Mice Translating Treatment-related toxicity Work abeta accumulation age related aging population apolipoprotein E-4 base cancer therapy cell injury comorbidity dentate gyrus genetic analysis genetic risk factor genetic variant improved mutant neurobehavioral neurotoxicity preservation prevent repaired tau Proteins tau mutation tissue injury treatment risk

项目摘要

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.

抽象的阿尔茨海默氏病（AD）和相关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。影响开发AD风险的遗传变异很普遍，可以用作生物标志物并能够开发在上下文中保护神经功能的广告特定方法其他与年龄有关的疾病的合并症和疗法可能会使神经系统定义更加复杂这发生在广告中。癌症是老龄化个体中重要且常见的合并症。使用AD模型，该提案研究了接受指示癌症疗法后可能发展的神经认知功能障碍对于大脑而言，其机制目前尚未理解。该提案调查了是否与神经退行性疾病相关的遗传因素倾向于个体在神经认知下的下降脑放射疗法。这项工作的结果将确定致病性之间的基本关系癌症治疗后AD和神经系统功能的基础过程可能会用于发展最小化治疗引起的AD或有AD风险的人的神经认知缺陷的策略。