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2019 Alzheimer's Association Research Grant (AARG)

Understanding the Impact of a Late-Onset Alzheimer's Disease Mutation in CD2AP on Synapses

How do genetic changes alter nerve cell communication in Alzheimer’s disease?

Claudia Almeida, Ph.D.
UNL - NOVA Medical School | Faculdade de Ciências Médicas - CEDOC
Lisbon, Portugal


Several genetic changes have been identified that can increase a person’s risk of late-onset Alzheimer’s disease. Among these changes include the CD2AP gene, responsible for producing a protein important for nerve cell function. CD2AP helps maintain structural support within the cell and also helps transport proteins inside nerve cells. Furthermore, CD2AP helps nerve cells communicate through specialized cell structures known as synapses. Recent studies have shown certain changes in the gene that produces CD2AP can harm synapses, and are associated with increased production of beta-amyloid protein that forms plaques, a hallmark of Alzheimer’s.
It is not clear exactly how changes in CD2AP lead to increased levels of beta-amyloid protein. Dr. Claudia Almeida believes that changes in CD2AP may affect its functionality and alter how beta-amyloid protein is transported inside nerve cells. Dr. Almeida proposes to investigate how these genetic changes in CD2AP damage synapses and impact levels of beta-amyloid plaques.

Research Plan

Dr. Almeida and colleagues will perform several studies in cells growing in laboratory dishes to understand how changes in CD2AP may harm synapses. To conduct their study, the researchers will be using mouse nerve cells and a special type of stem cell from human adult tissue, called iPSCs (induced Pluripotent Stem Cells). iPSCs can be programmed to grow into any type of cell in the human body. The researchers will use iPSCs to create nerve cells in laboratory dishes. Using these different cell models, Dr. Almeida will study how genetic changes similar to those found in people with late onset Alzheimer’s disease affect synapse shape and function. Cutting-edge brain scan and biochemical techniques will enable Dr. Almeida and her team to also track beta-amyloid accumulation and test strategies to protect synapses in their experimental models.


The study results could help inform mechanisms by which genetic changes in CD2AP associated with late onset Alzheimer’s disease drives dysfunction in nerve cell communication. Additionally, if CD2AP associated brain changes can be reversed, it could unlock a novel treatment pathway for Alzheimer’s disease.

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