Today’s Solutions: November 30, 2021

A breakthrough study from Sanford Burnham Prebys, has uncovered some of the mysteries surrounding the brains of individuals with Down syndrome. The disorder occurs when people obtain an extra copy of chromosome 21, giving them three instead of two. With one in 700 births carrying this chromosomal disorder, it is the most common birth disorder impacting humans.

Being born with Down syndrome leads to lasting cognitive problems and often the development of Alzheimer’s disease in the individual’s 40s. Previous research has identified some of the genes and biochemical pathways responsible for this process, though the molecular changes leading up to the event are unclear.

Old techniques used in a new way

The research team carried out genetic studies on 29 post-mortems Down syndrome brains, analyzing RNA molecules using a method called single-nucleus transcriptomics. This technique has been applied to research in many other diseases to uncover their inner workings, but never in Down syndrome research.

They also used long-read sequencing, a highly accurate genome analysis that has never been carried out in the human brain before. “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,” said Jerold Chun, lead author of the paper. “These can now be considered toward understanding the brain.”

Understanding the Down syndrome brain

A number of molecular characteristics were uncovered from the study, giving numerous clues as to why Alzheimer’s disease frequently reveals itself. It was found that specific types of neurons and RNA molecules associated with neurodegeneration were found in abundance in the brains.

Also, a high number of microglia was found to be activated and present. These are a type of cell associated with common forms of Alzheimer’s, which are also becoming an emerging target for treatment. “We could see these microglial features in young brains, well before Alzheimer’s occurs,” says Chun. “This finding identifies microglia as a prominent and early player in the Down syndrome brain.”

The future of treatment

This first look into the neuronal inner workings of Down syndrome is a huge step forward in the field of both this chromosomal disorder and also into Alzheimer’s research. Chun added, “It’s wonderful that people with Down syndrome are living longer now than at any point in history, and we hope our research ultimately contributes to their improved quality of life at all ages.”

Source study: Proceedings of the Nationwide Academy of Science – Altered cell and RNA isoform diversity in aging Down syndrome brains

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