Analysis of human brain tissue reveals differences in how immune cells behave in Alzheimer's disease brains compared to healthy brains, pointing to potential new therapeutic targets.
This was revealed in a study led by the University of Washington published in August. microglia In the brains of Alzheimer's patients, in a pre-inflammatory state More often, they are less likely to defend.
Microglia are immune cells that help maintain brain health by removing waste products and maintaining normal brain function.
In response to infection or to clear out dead cells, these nifty shape-shifters become thinner and more mobile to engulf intruders and debris.they too “Pruning” synapses during developmentit helps our brain form circuits to function well.
The role of microglia in Alzheimer's disease is less clear, but in people with severe neurodegenerative diseases, some microglia respond very strongly and may cause inflammation It contributes to the death of brain cells.
Unfortunately, in clinical trials, Anti-inflammatory drugs for Alzheimer's disease show no significant effect.
To take a closer look at the role of microglia in Alzheimer's disease, University of Washington neuroscientists Katherine Prater and Kevin Green, along with colleagues from multiple institutions in the United States, teamed up with research partners (12 patients with Alzheimer's disease and healthy controls) to study the role of microglia in Alzheimer's disease. The genes were studied using brain autopsy samples from 10 people. Microglial activity.
Enhance using new methods mononuclear RNA sequencingThe research team was able to precisely identify 10 distinct clusters of microglia in brain tissue based on their unique set of gene expressions that tell the cells what to do.
TThree of the clusters had never been seen before, and one was more common in Alzheimer's patients. This type of microglia has genes involved in inflammation and cell death turned on.
Overall, the researchers found that microglial clusters in the brains of Alzheimer's patients were likely microglial clusters in a pre-inflammatory state.
This means they are more likely to produce inflammatory molecules that can damage brain cells and contribute to the progression of Alzheimer's disease.
The types of microglia in the brains of Alzheimer's patients are less likely to exert protective functions, impairing their ability to withstand weight in removing dead cells and waste products and promoting healthy brain aging. There is.
Scientists also believe that microglia may change types over time. Therefore, just by looking at a person's brain, we cannot say with certainty which type of microglia a person has. Tracking how microglia change over time may help understand how microglia contribute to Alzheimer's disease.
“At this point, we don't know whether microglia are driving the disease state or whether the disease state is changing the behavior of these microglia.” Said Prater.
Although this research is still in its early stages, it advances our understanding of the role of these cells in Alzheimer's disease and suggests that specific microglial clusters may represent new therapeutic targets.
The researchers hope their research will lead to the development of new treatments that can improve the lives of Alzheimer's patients.
“Now that we know the genetic profile of these microglia, we can examine exactly what they are doing and hopefully identify ways to change their behavior, which may be contributing to Alzheimer's disease. ,” says Dr. Prater. Said.
“If we can identify what they are doing, we may be able to change their behavior with treatments that can prevent or slow the disease.”
This study natural aging.
A previous version of this article was published in August 2023.
