2024 Alzheimer's Association Research Fellowship (AARF)

The role of myelin in Alzheimer's Disease

Is myelin involved in Alzheimer’s brain changes?

Marios Georgiadis, Ph.D.
Stanford University School of Medicine
Stanford, CA - United States

Background

The brain communicates through a series of “networks” which connect multiple brain regions. These networks have control over different types of cognitive functions, including memory. Brain changes that may happen as a result of aging or as a result of disease, such as Alzheimer’s, may impact how nerve cells communicate with one another.  Nerve cells use long, thread-like extensions called axons to “talk” to other brain cells. In Alzheimer’s disease and related dementias, however, these axons become damaged, a process that disrupts cell-to-cell communication and contributes to memory loss and other forms of cognitive (brain function) decline. One important aspect of these axons that may become damaged during disease is myelin. Myelin is a protective layer that wraps around the axons of nerve cells in the nervous system and is important for the proper function of nerve cells.

Research Plan

To understand the impact on myelin in Alzheimer's, Dr. Georgiadis and colleagues will use specialized imaging techniques to make 3-dimensional maps of myelin in the hippocampus, a brain region important for learning and memory. This will allow the research team to understand how myelin changes in Alzheimer’s. 

The researchers will then use a new approach that combines multiple, advanced, computational techniques known as “multiple omics analyses''.For example, this includes combining lipidomics - the study of how lipids (fats) are used by the cell, proteomics - the study of the structure and functions of proteins made by cells, and transcriptomics - the study of how gene activity is turned “on” or “off” within a cell. This technique will allow the research team to explore the underlying biological mechanisms associated with changes in myelin observed previously in the 3-dimensional maps.

Finally, the research team will use a specialized imaging technique to compare how changes in myelin interact with hallmark brain changes in Alzheimer’s including the accumulation of the proteins beta-amyloid and tau into abnormal plaques and tangles, respectively.

Impact

Results from this study may help researchers understand the impact of myelin in the brain and develop myelin-related biological markers (biomarkers) to improve diagnosis, further research, and treatment opportunities.