2024 Alzheimer's Association Research Grant to Promote Diversity (AARG-D)
Dosage effect of APP to induced neuronal degeneration in Down syndrome
What are the mechanisms that contribute to Alzheimer’s risk in individuals with Down syndrome?
Lucas Sosa, M.D., Ph.D.
Centro de Investigaciones en Química Biológica de Córdoba - CIQUIBIC
Córdoba, Argentina
Background
Individuals with Down syndrome are at a high risk for developing Alzheimer’s. By the early age of 40, most individuals with Down syndrome have amyloid plaques and tau tangles in their brains, both of which are hallmark brain changes observed in Alzheimer’s. Studies have shown that amyloid plaque buildup occurs before the formation of tau tangles. However, the mechanisms by which this occurs and its link to Alzheimer’s risk for people living with Down syndrome are unknown.
Research Plan
For their project, Dr. Lucas Sosa and colleagues will examine how amyloid plaques lead to tau tangle formation and Alzheimer’s progression in Down syndrome. To do this, they will use a specialized type of stem cell collected from adult human tissue called induced Pluripotent Stem Cells (iPSCs), which can be programmed into any type of cell in the body, including nerve cells, and grown in a laboratory dish. The iPSCs used for this study will be collected from cells of individuals with Down syndrome. The researchers will first expose the iPSCs to increasing levels of amyloid precursor protein, the molecule that produces beta-amyloid and ultimately amyloid plaques, and measure how tau tangles are changed. Next, the team will examine how APP levels impact genetic variations that contribute to Alzheimer’s risk and disease progression.
Impact
The results of this study could shed new light on the mechanisms that contribute to Alzheimer’s risk in individuals with Down syndrome. The findings could also lead to the development of early-stage diagnostic methods and therapies for Alzheimer’s in this population.