Neurophysiological Assessments of Network Dysfunction in Alzheimer's Disease

阿尔茨海默病网络功能障碍的神经生理学评估

• 批准号: 10377356
• 负责人: Kamalini Gayathree Ranasinghe
• 金额: $ 17.12万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10377356
• 关键词: Age; Aging; Alzheimer' s Disease; Alzheimer' s disease model; Alzheimer' s disease patient; Amyloid beta-Protein; Anatomy; Animal Model; Architecture; Behavioral; Biological Markers; Biometry; Brain; Brain imaging; California; Clinical; Clinical Research; Clinical Trials; Cognition; Cognitive; Cognitive aging; Cognitive deficits; Data; Dementia; Deposition; Development; Disease; Disease Progression; Environment; Evaluation; Frequencies; Functional disorder; Future; Goals; Grant; Human; Impaired cognition; Impairment; Investigation; K-Series Research Career Programs; Knowledge; Link; Magnetoencephalography; Measures; Medial; Memory; Mentors; Molecular; Nerve Degeneration; Neurobiology; Neurodegenerative Disorders; Neurologist; Neurons; Neurosciences; Pathologic; Patients; Pattern; Physicians; Play; Positioning Attribute; Positron-Emission Tomography; Process; Proteins; Research; Research Ethics; Research Institute; Research Personnel; Research Project Grants; Research Training; Rest; San Francisco; Scientist; Spatial Distribution; Synapses; Synaptic plasticity; Syndrome; Techniques; Temporal Lobe; Testing; Therapeutic Intervention; Tracer; Training; Translational Research; Universities; Work; Writing; abeta accumulation; abeta deposition; base; brain behavior; career; career development; cognitive ability; design; experience; follow-up; imaging study; innovation; insight; knowledge base; molecular imaging; molecular marker; multimodal neuroimaging; multimodality; network dysfunction; neural circuit; neural patterning; neurobehavioral; neurodegenerative dementia; neuroimaging; neuronal circuitry; neurophysiology; neuroregulation; novel; progressive neurodegeneration; relating to nervous system; spatiotemporal; targeted treatment; tau Proteins; tau aggregation; treatment strategy; uptake

PROJECT SUMMARY This is an application for a K08 Mentored Clinical Scientist Research Career Development Award to promote the candidate's development as an independent researcher in clinical neuroscience, with a focus on understanding the neurophysiological abnormalities in Alzheimer's disease (AD), and eventually, in other dementia syndromes. Dr. Ranasinghe's long-term career goal is to develop a deep knowledge base on brain- behavior relationships associated with specific pathophysiological processes in neurodegenerative diseases. The current research project proposes a multimodal, longitudinal brain imaging study, integrating magnetoencephalographic imaging (MEGI) with positron emission tomography (PET), and with progressive trajectories of neurodegenerative processes, in AD patients. AIM-1 examines the distinct patterns of network synchronization deficits in patients with AD using MEGI, and their specific associations to PET-derived molecular markers of amyloid beta and tau. AIM-2 conducts longitudinal MEGI assessments of network deficits combined with cognitive and volumetric measures with annual follow-ups for two years. The results will uncover neurophysiological signatures of aberrant neuronal functions in AD, in humans, and will have important implications for translational research and clinical trials. This K08 will provide Dr. Ranasinghe with the support necessary to accomplish the following goals: (1) Training in application and analysis of multimodal neuroimaging techniques; (2) Clinical training in patient evaluations and longitudinal follow-up; (3) Gaining greater depth of knowledge in mechanisms of AD; (4) Training in advanced biostatistical analyses in clinical research; (5) Training in grant writing, career development, and research ethics. To achieve these goals, Dr. Ranasinghe has assembled a mentoring team including her primary mentor: Dr. Katherine Rankin (a neuropsychologist with expertise in neurodegenerative diseases); and two co-mentors: Drs. Gil Rabinovici (a behavioral neurologist with expertise in molecular imaging), and Srikantan Nagarajan (a neuroscientist with expertise in magnetoencephalography). The collaborators of Dr. Ranasingh'e project include Drs. Maria Luisa Gorno-Tempini (a behavioral neurologist with expertise in neuroimaging), Joel Kramer (a neuropsychologist with expertise in cognitive ageing), Lea Grinberg (a neuropathologist with expertise in neurobiology of AD), and Maria Glymour (a biostatistician). The candidate is a physician-scientist with a strong commitment to a career in neurodegenerative dementia research. The University of California San Francisco Memory and Aging Center is an ideal environment for the proposed training, being a top dementia research institute in the nation with access to world leading experts in clinical and translational research. The research and training experience described in this proposal will enable the candidate's goal of developing a strong independent research career in the field of neurophysiological assessments in neurodegenerative diseases.

项目总结 这是一份K08临床科学家导师研究职业发展奖的申请书，以促进 候选人作为临床神经科学独立研究员的发展，重点是 了解阿尔茨海默病(AD)的神经生理异常，并最终在其他 痴呆症。拉纳辛哈博士的长期职业目标是建立关于大脑的深厚知识基础-- 神经退行性疾病中与特定病理生理过程相关的行为关系。 目前的研究项目提出了一种多模式的纵向脑成像研究，将 使用正电子发射断层扫描(PET)的脑磁图成像(MEGI)和渐进式 阿尔茨海默病患者神经退变过程的轨迹。AIM-1研究了网络的不同模式 MEGI在AD患者中的同步性缺陷及其与正电子发射计算机断层显像的特异性关联 淀粉样β蛋白和tau蛋白的分子标记。AIM-2对网络缺陷进行纵向MEGI评估 结合认知和容量测量，每年随访两年。结果将会是 在人类中发现阿尔茨海默病患者异常神经元功能的神经生理特征，并将 对转化性研究和临床试验的重要影响。这款K08将为拉纳辛哈博士提供 实现以下目标所需的支助：(1)多式联运应用和分析方面的培训 神经影像技术；(2)患者评估和纵向随访的临床培训；(3)获得 对阿尔茨海默病的发病机制有更深入的了解；(4)临床高级生物统计分析培训 研究；(5)赠款编写、职业发展和研究道德方面的培训。为了实现这些目标，Dr。 拉纳辛格组建了一个指导团队，其中包括她的主要导师：凯瑟琳·兰金博士(A 和两位共同导师：Gil Rabinovici博士(a 具有分子成像专业知识的行为神经学家)和Srikantan Nagarajan( 在脑磁图方面的专业知识)。Ranasingh‘e博士项目的合作者包括Maria Luisa博士 Gorno-Tempini(在神经成像方面有专长的行为神经学家)，Joel Kramer(神经心理学家 Lea Grinberg(具有AD神经生物学专长的神经病理学家)，以及 玛丽亚·格拉摩(生物统计学家)。应聘者是一名内科科学家，对事业有着强烈的承诺。 在神经退行性痴呆的研究中。加州大学旧金山分校记忆与衰老 中心是建议培训的理想环境，是全国顶级痴呆症研究机构 能够接触到世界领先的临床和转化研究专家。研究和培训 本提案中描述的经验将使候选人发展强大的独立性的目标成为可能 在神经退行性疾病的神经生理评估领域的研究生涯。