Brain Autopsies Reveal a Potential New Culprit Behind Alzheimer’s Disease : ScienceAlert

Analysis of human brain tissue has revealed differences in how immune cells behave in Alzheimer’s disease brains compared to healthy brains, indicating a potential new target for treatment.

Research from the University of Washington, published in August, found that microglia in the brains of people with Alzheimer’s disease were in a pre-inflammatory state more frequently, making them less likely to be protective.

Microglia are immune cells that help keep our brains healthy by removing waste and maintaining normal brain function.

In response to infection or to remove dead cells, these clever shapeshifters can become less spindly and more mobile to gobble up invaders and waste. They also “prune” synapses during development, which helps shape the circuits needed for our brains to function properly.

It’s unclear what role they play in Alzheimer’s disease, but in people with this devastating neurodegenerative disease, some microglia react too strongly and can cause inflammation that contributes to brain cell death.

Unfortunately, clinical trials of anti-inflammatory drugs for Alzheimer’s disease have not shown significant effects.

To study the role of microglia in Alzheimer’s disease, neuroscientists Katherine Prater and Kevin Green of the University of Washington, along with their colleagues at several US institutions, used brain autopsy samples from research donors – 12 with Alzheimer’s disease and 10 healthy controls – to study the gene. microglia activity.

Using a new method to improve mononuclear RNA sequencing, the team was able to deeply identify 10 different groups of microglia in brain tissue based on their unique set of gene expression, which tells cells what to do.

TThree of these groups had never been seen before, and one of them was more common in people with Alzheimer’s disease. This type of microglia has activated genes that are involved in inflammation and cell death.

Overall, the researchers found that the clusters of microglia in the brains of people with Alzheimer’s disease were more likely to be those in a pre-inflammatory state.

This means they were more likely to produce inflammatory molecules that could damage brain cells and possibly contribute to the progression of Alzheimer’s disease.

The types of microglia found in the brains of people with Alzheimer’s disease were less likely to be protective, compromising their ability to do their part to clean up dead cells and waste and promote healthy brain aging.

Photomicrograph of microglia (green) from a brain with Alzheimer’s disease. (Lexi Cochoit/UW Neuroinflammation Lab)

Scientists also believe that microglia can change their type over time. So we can’t just look at a person’s brain and say with certainty what type of microglia they have; Tracking the evolution of microglia over time could help us understand how they contribute to Alzheimer’s disease.

“At this point, we can’t say whether microglia are causing the pathology or whether the pathology is causing these microglia to change their behavior,” Prater said.

This research is still in its early stages, but it advances our understanding of the role of these cells in Alzheimer’s disease and suggests that certain groups of microglia could be targets for new treatments.

The team hopes their work will lead to the development of new treatments that could improve the lives of people with Alzheimer’s disease.

“Now that we have determined the genetic profiles of these microglia, we can try to find out exactly what they are doing and hopefully identify ways to change their behaviors that could contribute to Alzheimer’s disease,” said Prater.

“If we can determine what they are doing, we may be able to change their behavior with treatments that can prevent or slow this disease.”

The study was published in Natural aging.

An earlier version of this article was published in August 2023.

News Source :
Gn Health

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