Neurodevelopment in children from families with genetic frontotemporal dementia and Alzheimer's disease

遗传性额颞叶痴呆和阿尔茨海默病家庭儿童的神经发育

基本信息

批准号：
10632707
负责人：
SUZEE EURIE LEE
金额：
$ 3.62万
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：
2022
资助国家：
美国
起止时间：
2022-02-15 至 2027-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10632707
关键词：
Adult Age Alzheimer&apos s Disease Amygdaloid structure Animal Model Attention Attention deficit hyperactivity disorder Behavioral Symptoms Bilateral Biological Markers Biology Brain Child Clinical Cognitive Corpus striatum structure Cross-Sectional Studies DNA Sequence Alteration Data Differential Diagnosis Disease Dominant Genes Dyslexia Family Family member Frontotemporal Dementia Functional Magnetic Resonance Imaging Genetic Human Inferior Insula of Reil Language Learning Disabilities Left Life Longevity Memory Modeling Mutation Neurobehavioral Manifestations Neurodegenerative Disorders Neurodevelopmental Disorder Pattern Performance Phase Play Primary Progressive Aphasia Resources Role Structure Symptoms Syndrome Work aged autism spectrum disorder autistic children base behavior measurement behavioral variant frontotemporal dementia disease-causing mutation early detection biomarkers executive function frontal lobe gray matter insight mutation carrier neural circuit neural network neurodevelopment neuroimaging presenilin-1 white matter young adult

项目摘要

Supplement Title: Neurodevelopment in children from families with genetic frontotemporal dementia and Alzheimer's disease Project summary/abstract: The current conceptualization of genetic frontotemporal dementia (FTD) and Alzheimer's disease (AD) is that they are neurodegenerative diseases with symptoms developing later in life. Yet, studies in animal models support the notion that autosomal dominant genes whose mutations cause these diseases play critical roles in neurodevelopment. Previous studies show that young adult presymptomatic carriers for FTD and AD mutations show detectable differences in the neural circuits that are also targeted during the symptomatic phase. It remains unknown how early these abnormalities start and the extent to which children with these mutations may show clinical overlap with neurodevelopmental disorders such as autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD), and language-based learning disabilities (LBLD). Studying children with FTD and AD mutations offers a unique model to evaluate lifelong neural circuit vulnerability since each disease targets distinct neural circuits. At the UCSF Dyslexia Center, we will cross-sectionally study children from families with a known genetic mutation for FTD or AD and compare them children with ASD, ADHD, and LBLD. Aims 1 and 2 will compare children carrying a genetic mutation for FTD and children carrying a genetic mutation for AD with noncarrier family members to identify differences in brain structure and neural network connectivity. Aim 3 will explore comparisons between mutation carriers and children with ASD, ADHD, and LBLD. Upon completion, we will have identified how early disease-specific neural circuit differences arise in genetic FTD and AD. These findings will reveal important insights into the underlying biology of these diseases and when biomarker differences develop during the lifespan for genetic FTD and AD.

补充标题：来自患有遗传额颞痴呆症患者的儿童神经发育阿尔茨海默氏病项目摘要/摘要：遗传额颞痴呆（FTD）和阿尔茨海默氏病（AD）的当前概念是它们是神经退行性疾病，其症状以后出现。但是，动物模型的研究支持这样的观念，即常染色体显性基因的突变引起这些疾病在神经发育。先前的研究表明，FTD和AD突变的年轻成人预症状载体在有症状阶段也针对的神经回路显示可检测的差异。它这些异常的早期以及这些突变的儿童在多大程度上尚不清楚可能显示出与自闭症谱系障碍（ASD）等神经发育障碍的临床重叠注意缺陷多动症（ADHD）和基于语言的学习障碍（LBLD）。研究 FTD和AD突变的儿童提供了一个独特的模型来评估终身神经电路脆弱性，因为每种疾病都针对不同的神经回路。在UCSF阅读障碍中心，我们将横截面研究来自FTD或AD的已知基因突变家庭的孩子，并将他们的孩子与ASD进行比较 ADHD和LBLD。 AIM 1和2将比较携带FTD遗传突变的儿童和儿童与非载体家族成员一起携带AD的遗传突变，以确定大脑结构的差异和神经网络连通性。 AIM 3将探索突变载体和ASD儿童之间的比较， ADHD和LBLD。完成后，我们将确定早期特异性神经回路遗传FTD和AD中出现差异。这些发现将揭示对基础的重要见解这些疾病的生物学以及生物标志物在遗传FTD和AD的生命周期中发生差异时。