Molecular Changes in Down Syndrome

Molecular changes within the aging brains of individuals with Down syndrome have been unraveled by the first study of its kind at the Sanford Burnham Prebys, published in the journal Proceedings of the National Academy of Science.

Down syndrome, also known as trisomy 21 is the most common chromosomal disorder. It occurs due to an extra copy of human chromosome 21 in the body, thus resulting in three copies instead of the usual two.

‘Molecular changes within the aging brains of individuals with Down syndrome have been unraveled by a study. ’

Down syndrome affects one in every 700 births. The disorder not only hampers cognition in patients but also makes them vulnerable to neurodegeneration later in life.

Down syndrome and Neurodegeneration

"By the time they're in their 40s, every single person with Down syndrome will experience some Alzheimer's pathology. We asked what happens in the brain before Alzheimer's disease takes hold," says senior author Jerold Chun, M.D., Ph.D., professor and senior vice president of Neuroscience Drug Discovery at Sanford Burnham Prebys.

The team was thus set to explore the cellular and molecular changes that are responsible for triggering the pathways behind this phenomenon. Nearly 29 post-mortems of Down syndrome brains were analyzed using a method called single-nucleus transcriptomics (to look at the RNA molecules within single cells).

It is known that RNA encodes for proteins. Thus, knowing the RNA sequence reveals which proteins are likely to be produced.

Brain Changes Revealed

"Our study revealed unappreciated changes in brain cell types involving hundreds of thousands of never-before-seen RNAs that can't be seen using standard techniques. These can now be considered toward understanding the brain," says, Chun.

It was found that in Down syndrome, overall there are more inhibitory (neurons that block the brain's electrical signals) than excitatory neurons in the brain.

Moreover, it was also found that there is early and sustained increases in activated microglia (type of brain immune cell) - one of the emerging target for treating common forms of Alzheimer's disease.

The presence of these differences may help explain the cognitive challenges of the patients suffering from Down syndrome and pave the way for new therapies to aid people with Down syndrome and Alzheimer's disease.

Source: Medindia