2023 Alzheimer's Association Research Fellowship (AARF)

Synaptic Dysfunction in Alzheimer's disease.

Can certain chemical processes in the brain help prevent the loss of cell-to-cell communication in Alzheimer’s?

Maria del Pilar Rivero Rios, Ph.D.
University of Michigan
Ann Arbor, MI - United States

Background

Nerve cells send signals to one another through specialized structures called synapses. Biological processes can change (modulate) the strength of synaptic signals, and some modulations are thought to enhance brain functions. One such modulation is a biological process called long term potentiation (LTP), which strengthens learning and memory. Scientists have found that individuals with Alzheimer’s show damage to synapses and impairments in LTP – problems that may lead to memory loss and brain cell death. Moreover, while it remains unclear exactly how such disease processes take place in Alzheimer’s, studies suggest they may be related to changes in the way nerve cells transport nutrients and other molecules within the cells. These changes involve series of chemical processes called “pathways.”  

In initial research, Dr. Maria del Pilar Rivero-Rios and colleagues have been studying whether a particular chemical pathway (called the SNX17 pathway) may be linked to synaptic health in Alzheimer’s. They found that after removing this pathway in brain cells, the cells developed a significant loss of synaptic activity and LTP They also found that SNX17 pathway activity was reduced in brain samples of individuals who had Alzheimer’s. Taken together, these findings suggest that the SNX17 pathway is critical for preventing Alzheimer’s-related synaptic dysfunction, brain cell damage and memory loss.

Research Plan

Dr. del Pilar Rivero-Rios and colleagues will conduct a larger study to confirm and expand on their earlier findings. First, they will determine whether proteins of the SNX17 pathway are reduced in brain samples of individuals and rodents who had Alzheimer’s, as well as in brain cells engineered from individuals with the disease. Next, using mouse nerve cells with reduced SNX17 pathway function, they will examine whether these cells are more susceptible to damage and death when exposed to beta-amyloid (a hallmark brain change in Alzheimer’s). Lastly, the researchers will  test whether increasing SNX17 pathway activity can prevent synaptic dysfunction in genetically engineered Alzheimer's-like mice.    

Impact

The results of this study could shed new light on how synaptic loss takes place in Alzheimer’s. They could also identify the SNX17 pathway as a target for future disease therapies.