Scientists have been trying to identify the exact causes of Alzheimer's disease for many years, and while we know that pathologies like tau tangles and amyloid plaques are related to the neurodegenerative disorder, there is still much that is unknown. Researchers have now identified a gene that is associated with Alzheimer's disease, and which could provide novel insights into how to treat the disease. The findings have been reported in The American Journal of Human Genetics.
Genes that are linked to Alzheimer's disease have previously been found using genome-wide association studies (GWAS). These connect small changes in the sequences of different genes with a disease. But these studies do not always find the biological basis for the association, or how changes to gene function are connected to Alzheimer's. This work aimed to reveal more about the function of an Alzheimer's associated gene called MTCH2.
The work used a fruit fly model to show how Alzheimer's risk increases due to changes in this gene. It also revealed that when changes in this gene are reversed, it has a neuroprotective influence.
"Alzheimer's disease affects more than 50 million people worldwide and although researchers have learned a great deal about it over the years, its causes are still not fully understood and effective therapies are not yet available," said corresponding study author Dr. Juan Botas, a professor at Baylor College of Medicine, among other appointments.
After the scientists found 123 candidate genes that were probably linked to Alzheimer's with the GWAS data, those predictions were tested, noted co-first study author Morgan C. Stephens, a graduate student in the Botas lab.
The researchers found that of 60 gene candidates that could be tested in fruit flies, there were 46 that affected neurons in their research models. When the activity of 18 of these genes was altered, the risk of Alzheimer's disease-related symptoms increased.
There were also eleven genes that could be altered to protect fruit flies from neurodegeneration.
"In the list of final candidates, MTCH2 turned up to be at the top in the functional studies," Stephens said. "MTCH2 expression is downregulated in human [Alzheimer's disease] brain samples, and reducing its function in flies aggravates motor dysfunction. It was very exciting to find that restoring MTCH2 expression in flies reversed motor dysfunction and reduced tau accumulation in human neural progenitor cells in the lab."
Now, MTCH2 could be a great candidate in the pursuit of medications that could treat Alzheimer's.
Sources: Baylor College of Medicine, American Journal of Human Genetics