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

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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.