Understanding Neurodevelopmental Origin of Alzheimer’s Disease Using Lifespan Approach
2025 Award: $198,959
Early-life development is characterized by dramatic changes, impacting lifespan function more than changes in any other period. Although the developmental origins of neurodegenerative diseases in later life are recognized, there is a lack of detailed longitudinal neuroimaging studies that link early development and brain maturation with the neurobiological mechanisms of dementia. We will answer the outstanding questions by capitalizing on large-scale neuroimaging data alongside environmental exposures and demographic information.
Need/Problem: Human brain development spans the first thirty years of life, with brain maturation during the first two decades playing a critical role in shaping its vulnerability to neurodegenerative diseases as we age. However, due to the absence of large-scale lifespan data ranging from childhood to late adulthood, our understanding of early-life dementia risk remains limited.
Grant Summary: We will implement a lifespan approach to fully understand (1) How do the cortical changes occurring across early childhood adolescence, and adulthood mirror the changes associated with dementia in later life? (2) What neurobiological mechanisms are associated with this lifespan mirroring? and (3) What are the social implications of a neurodevelopmental origin that we can leverage to design improved interventions and therapeutic strategies for preventing AD?
Goals & Projected Outcomes: We expect that the success of this project will carry important social implications, underscoring the notion that Alzheimer’s should be viewed as a lifespan disease rather than merely an age-related condition.
Guorong Wu, PhD
Marissa DiPiero, PhD
Grant Details: First, we will apply a systems biology model to establish a system-level understanding of rapid cortical changes in brain development and the complex neurodegeneration process in Alzheimer’s disease, with a focus on the impact of childhood adversity experience on late-life neurodegeneration. Second, we will explore the biological mechanism that explains the presence of lifespan mirroring patterns. Specifically, we will investigate whether a shared neurobiological mechanism underlies cortical changes in both early life and aging brains. Third, we will clarify the early-life social determinants contributing to the increased risk of dementia in later life, which might have a critical role in the health disparities in AD. In this context, we will focus on examining how low maternal educational attainment in youth impacts dementia risk in midlife.
