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Trajectories and Markers of Neurodegeneration in Fragile X Premutation Carriers

脆性 X 前突变携带者神经变性的轨迹和标志物

基本信息

批准号：
10417064
负责人：
DAVID R HESSL
金额：
$ 61.24万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-06-01 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10417064
关键词：
Address Affect Age Alternative Splicing Ataxia Autonomic Dysfunction Behavior Behavioral Biological Biological Markers Brain Clinic Clinical Clinical Trials Collection Data Dementia Deterioration Development Diagnosis Diastolic blood pressure Dietary Fiber Disease Disease Marker Disease Progression Domestic Fowls Early Intervention Equilibrium Equipment and supply inventories Exercise Exhibits FMR1 FMR1 Premutation FXTAS Fabaceae Fatty acid glycerol esters Fishes Food Fragile X Premutation Funding Future Gait Gait Ataxia Gene Expression Gene Expression Profile Genetic Markers Goals Health High Prevalence Home Individual Intake Intention Tremor Intervention Life Life Style Longitudinal Studies Manuals Measurement Measures Mental disorders Messenger RNA Molecular Motor Movement Movement Disorder Society Unified Parkinson&apos s Disease Rating Scale Nerve Degeneration Nervous System Physiology Neurodegenerative Disorders Neurologic Neurologic Examination Neuropsychology Nutritional Nuts Parkinsonian Disorders Penetrance Peripheral Nervous System Diseases Phenotype Pontine structure Population Prevention Process Protein Isoforms Protocols documentation Research Risk Risk Factors Severity of illness Short-Term Memory Speed Structure Symptoms Task Performances Testing Time To specify Tremor Visual White Matter Hyperintensity Width age related brain morphology clinical examination cohort executive function fruits and vegetables lifestyle factors male medical examination men men&apos s group mild cognitive impairment molecular marker motor control nervous system disorder neuroimaging neuroimaging marker predictive marker prevent programs prospective protective factors resilience response sugar

项目摘要

FMR1 premutation carriers exhibit mild cognitive impairment and have an increased rate of psychiatric disorders. Critically, they are at risk for developing a neurodegenerative disease, fragile X-associated tremor/ataxia syndrome (FXTAS), which is characterized by progressive gait ataxia, intention tremor, Parkinsonism, dementia, autonomic dysfunction, peripheral neuropathy and key neuropathological features. The disease has a variable and age-related penetrance, affecting 75% of male premutation carriers by the eighth decade of life. Given the high prevalence of the FMR1 premutation in the population (about 1/468 males) this is a significant health issue that affects a large number of individuals. There is currently no treatment for FXTAS and no empirically evaluated interventions to prevent or slow the disease progression. Importantly, no biological or behavioral markers are available for predicting which premutation carrier will develop FXTAS before the clinical symptoms appear. In the last funding period of our program of research (“Trajectories and Markers of Neurodegeneration in Fragile X Premutation Carriers”) we have successfully followed FMR1 premutation carriers and age-matched controls for at least two, and in some cases 3 longitudinal time points, obtaining neuroimaging, neuropsychological, and molecular measurements as well as medical and neurological examinations. We have identified neuroimaging, behavioral and molecular markers that show promise for predicting, before the onset of clinical symptoms, which premutation carriers will convert to FXTAS, and for tracking changes during the early stages of disease. Ours remains the only prospective, longitudinal study of FMR1 premutation carriers being conducted, and understanding the prodrome of FXTAS remains critical for the early intervention and prevention of this neurodegenerative disease. For the current project, we will continue to collect longitudinal neuroimaging, neuropsychological and molecular data from our existing cohort and a new cohort of carriers and controls with an overarching goal to define the prodrome of FXTAS, refining our protocol in accordance with what we learned in the last five years, and adding biomarkers and clinically sensitive measures and assessments of lifestyle factors to better address hypotheses about risk and resilience in this population.

FMR1预突变携带者表现出轻度认知障碍，并有增加的发病率

项目成果

期刊论文数量（19）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Fragile X-associated tremor/ataxia syndrome: another phenotype of the fragile X gene.

DOI：
10.1080/13854046.2016.1186661
发表时间：
2016-08
期刊：
The Clinical neuropsychologist
影响因子：
0
作者：
Hessl D;Grigsby J
通讯作者：
Grigsby J

Young adult male carriers of the fragile X premutation exhibit genetically modulated impairments in visuospatial tasks controlled for psychomotor speed.

DOI：
10.1186/1866-1955-4-26
发表时间：
2012-11-13
期刊：
Journal of neurodevelopmental disorders
影响因子：
4.9
作者：
Wong LM;Goodrich-Hunsaker NJ;McLennan Y;Tassone F;Harvey D;Rivera SM;Simon TJ
通讯作者：
Simon TJ

Using an Isogenic Human Pluripotent Stem Cell Model for Better Understanding Neurodevelopmental Defects in Fragile X Syndrome.

使用同基因人类多能干细胞模型更好地了解脆性 X 综合征的神经发育缺陷。