2021 Alzheimer's Association Research Grant (AARG)

Identification of RNA-Binding Protein Networks in Alzheimer’s disease

How do proteins in the brain impact the dysfunction of brain cell communication in Alzheimer’s?

Kimberly Raab-Graham, Ph.D.
Wake Forest University
Winston-Salem, NC - United States

Background

In the brain, nerve cells communicate through specialized structures called “synapses” that connect one nerve cell to another. These synapses contribute to memory formation by increasing levels of specific proteins that help to form and save a memory. Studies show that synapses may become damaged in Alzheimer’s, impacting the nerve cell communication networks. This may contribute to the memory loss during Alzheimer’s. 
 
In previous work, Dr. Kimberly Raab-Graham and colleagues identified two proteins at the synapses that stop working properly in the brains of individuals who had Alzheimer’s. Their findings suggest that these two proteins, called DJ-1 and FMRP (Fragile X Mental Retardation Protein), may contribute to the formation, stability, and functioning of synapses. Dr. Raab-Graham believes that a loss of the proper function of these proteins may influence the loss of memories during the progression of Alzheimer’s.
 

Research Plan

Dr. Raab-Graham and her colleagues will study how the proteins DJ-1 and FMRP impact synaptic function in Alzheimer’s. The researchers will use advanced molecular techniques to investigate the gene networks associated with these proteins in two model systems designed to mimic the brain changes in Alzheimer’s and allow the research team to study the impact of the synaptic function. They will verify their findings in brain tissue from individuals who had Alzheimer’s. In addition, Dr. Raab-Graham and her team will study the biological underpinnings by which these proteins impact synaptic function.

Impact

If successful, the results of this project may shed light on how synaptic dysfunction occurs in Alzheimer’s. The findings may help identify new targets and avenues for the treatment or prevention of Alzheimer’s.