A New Discovery May Translate to New Treatment for Alzheimer’s Disease
Posted on March 31, 2018
A new study shows promise for treating and possibly preventing Alzheimer’s disease.
The study, conducted by the University of Washington Health Sciences/UW Medicine, shows that improving how cellular proteins move within brain cells may prevent the body from producing the toxic amyloid beta protein and Tau protein.
Both amyloid beta protein and Tau protein are thought to cause brain cell death associated with Alzheimer’s disease and other forms of dementia by forming plaques in the brain cells that interfere with normal brain function.
Alzheimer’s disease is a progressive disease that worsens over time. Alzheimer’s disease affects over 5 million Americans and can cause memory loss, forgetfulness, cognitive impairment and confusion.
The UW Medicine study proposes that these toxic proteins build up in the brain because of a problem in the system responsible for moving proteins within a cell. Amyloid beta and Tau proteins move within the cell inside membrane-bound compartments known as endosomes.
The cellular system that moves the protein-filled endosomes around the cell is known as the endosomal network. For amyloid beta and Tau proteins to be processed by the cell correctly, the endosomal network must function properly.
Using human skin cells, the UW Medicine team found that by using a specialized compound called R33, they could enhance the operation of the endosomal network. This improved functioning and significantly reduced the creation of the amyloid beta protein and a precursor of the Tau protein.
During the study, the researchers collected skin cells from individuals with Alzheimer’s disease and individuals without the condition. As all individuals’ cells contain the same genetic information, the skin cells of those individuals with Alzheimer’s disease would have the same genetic mutations in their brain cells.
The next step in the study was to reprogram the skin cells to act as stem cells.
“Stem cells are the most basic, fundamental cells of the body with the unique ability to develop into many different types of cells,” said Dr. Joel Singer.
Singer is a New York physician who uses personal cells to treat patients living with neurological, orthopedic and autoimmune conditions.
“Due to their ability to change into different cell types, personal cells are very useful for treating a range of health conditions,” Singer said.
Once the cells were reprogrammed into stem cells, the UW researchers were able to create nerve cells that had the same genetic composition as the collected skin cells.
These new stem-cell neurons had the same likelihood of creating excess toxic amyloid beta and Tau protein precursor as the brain cells of individuals with Alzheimer’s disease.
The researchers measured the amount of amyloid beta and Tau protein in the new neural cells. Their next step was to see if they could improve how the endosomal network of these cells functioned by adding the R33 to the cells with increased amyloid beta and Tau protein.
The R33 acted positively on the retromer, the protein responsible for directing the delivery of the endosomal packages to the parts of the cell, which led to a reduction in the development of both the amyloid beta and the form of tau protein known as phosphorylated-Tau.
Researchers also tested the theory that increased production of the amyloid beta protein raises the production of phosphorylated-Tau.
The connection between the proteins indicates that using the R33 compound may mean a potential new treatment to reduce the buildup of these toxic proteins and a way to help treat or prevent Alzheimer’s disease.
University of Washington Health Sciences/UW Medicine. “Stem-cell study points to new approach to Alzheimer’s disease: An experimental compound reduced production of toxic proteins implicated in brain-cell death in Alzheimer’s disease.” ScienceDaily. ScienceDaily, 1 March 2018.