Examination of the earliest symptoms and biomarkers of FTLD MAPT carriers

FTLD MAPT 携带者最早症状和生物标志物的检查

• 批准号: 8548422
• 负责人: STEPHANIE Ann COSENTINO
• 金额: $ 41.38万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-21 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8548422
• 关键词: Accounting; Addictive Behavior; Age; Alcohol or Other Drugs use; Alcohols; Anterior; Behavior; Behavioral; Biological; Biological Markers; Brain; Cerebrospinal Fluid; Chromosomes; Chromosomes, Human, Pair 17; Clinical; Cognition; Cognitive; Collection; Controlled Environment; Data; Deposition; Detection; Diet; Disease; Early Diagnosis; Evaluation; Exons; Family; Frequencies; Frontotemporal Dementia; Frontotemporal Lobar Degenerations; Gene Mutation; Generations; Genes; Genetic; Genetic screening method; Grant; Image; Individual; Institutes; Life; Life Style; Link; Longitudinal Studies; Measures; Modality; Multivariate Analysis; Onset of illness; PGRN gene; Pattern; Physical activity; Plasma; Proteins; Recruitment Activity; Research Personnel; Sensitivity and Specificity; Specimen; Staging; Symptoms; Syndrome; Temporal Lobe; Therapeutic; Time; base; behavior test; cingulate gyrus; cohort; executive function; follow-up; gray matter; improved; lifestyle factors; member; mutation carrier; neuroimaging; offspring; public health relevance; recreational drug use; social cognition; tau Proteins; tau mutation; tool; white matter

DESCRIPTION (provided by applicant): Discoveries about the genetic bases of frontotemporal lobar dementia (FTLD) have provided researchers with an unprecedented ability to characterize the pre-symptomatic stages of this disease. This capability is critical to ascertaining the earliest clinical features of the disease and identifying biomarkers that can be used for early diagnosis and in treatment studies. The proposed project will examine individuals from a single family with a genetic mutation for FTLD who are approaching the age of disease onset, offering a unique and highly controlled environment in which to identify the earliest clinical features and biomarkers of this devastating disease. Specifically, this study proposes to follow the offspring generation of a large family with a known mutation in the MAPT (tau) gene to determine the earliest clinical features of FTLD and the variables which may modify disease onset and course. At least 90 members of the offspring generation of a single family will be offered participation in a longitudinal study examining cognition, behavior, psychiatric symptoms, and lifestyle features. Moreover, this proposal includes the use of state of the art neuroimaging tools including both structural and functional modalities, gray and white matter quantification, and regional and network analyses to detect the earliest signs of disease. Individuals will undergo genetic testing to determine carrier status, will be comprehensively characterized at baseline, and will be followed annually over the course of the study to examine change in clinical and imaging variables over time as a function of carrier status. Additionally, the proposed study will carefully characterize lifetime physical activity and alcohol and recreational drug use to determine if these lifestyle variables are early manifestations of disease and / or modify disease onset and course. Finally, biological specimens including cerebrospinal fluid and blood plasma will be longitudinally collected in an effort to characterize changes in brain protein levels that may provide early information regarding the onset and course of disease.

描述（由申请人提供）：关于额颞叶痴呆（FTLD）遗传基础的发现为研究人员提供了前所未有的能力来表征这种疾病的症状前阶段。这种能力对于确定疾病的早期临床特征和识别可用于早期诊断和治疗研究的生物标志物至关重要。拟议的项目将检查来自单一家庭的FTLD基因突变个体，这些个体接近疾病发病年龄，提供一个独特和高度控制的环境，以确定这种毁灭性疾病的早期临床特征和生物标志物。具体来说，本研究建议对一个已知MAPT （tau）基因突变的大家族的后代进行跟踪研究，以确定FTLD的早期临床特征以及可能改变疾病发病和病程的变量。一个家庭的至少90名后代将参与一项纵向研究，研究认知、行为、精神症状和生活方式特征。此外，该建议包括使用最先进的神经成像工具，包括结构和功能模式，灰质和白质量化，以及区域和网络分析，以发现疾病的最早迹象。个体将接受基因检测以确定携带者状态，将在基线时进行全面表征，并将在研究过程中每年进行随访，以检查临床和影像学变量随时间的变化作为携带者状态的函数。此外，拟议的研究将仔细描述终生体育活动、酒精和娱乐性药物使用的特征，以确定这些生活方式变量是否是疾病的早期表现