Researchers at the Mount Sinai School of Medicine in New York City have achieved an unprecedented understanding of how Alzheimer’s disease develops and grows, opening the way to treatments for the disease that affects millions around the world.
The researchers discovered the genetic and molecular mechanism in human microglia, which are the immune cells found in the brain. Discovering this mechanism could provide valuable insights into how the disease grows and progresses.
The results of the study were published in the journal Nature Genetics.
Working on fresh human brain tissue from 150 donors, the researchers identified 21 candidate genes that increase the risk of this disease and highlighted one gene, SPI1, as a potential key regulator of microglia and Alzheimer’s risk.
“Our study is the largest analysis of human tissue microglia to date for genetic risk factors that may predispose a person to Alzheimer’s disease,” says senior author Panos Roussos, professor of psychiatry and genetic and genomic sciences at the Icahn School of Medicine in Mount Sinai in New York. “With a better understanding of the molecular and genetic mechanisms associated with microglia function, we are in a much better position to unravel the regulatory landscape that controls this function and contributes to Alzheimer’s disease. This knowledge, in turn, could pave the way for new therapeutic interventions for an uncured disease.” Active at the moment.
Microglia are primarily responsible for the immune response in the brain, and are also important in developing and maintaining neurons. While previous studies have identified microglia as playing a major role in genetic risk and the development of Alzheimer’s disease, little is known about the epigenetic mechanisms of how this occurs. Because microglia are difficult to isolate within the human brain, most previous studies have used animal or cell-based models that do not reflect the true complexity of the function of microglia in the brain.
The solution the Mount Sinai Hospital team came up with was access to new brain tissue from biopsies or autopsies.
“Using a total of 150 samples from these sources, we were able to isolate high-quality microglia, which provided unprecedented insights into genetic regulation by reversing the full range of regulatory components of microglia in healthy and neurodegenerative patients,” Dr. Roussos explains. Neurodegeneration (neurolysis or neurodegeneration) is the progressive and progressive loss of structure or function of nerve cells, according to Wikipedia.
This process, which involved comparing epigenetics, gene expression, and genetic information from samples of both Alzheimer’s patients and healthy elderly subjects, allowed the researchers to describe how the functions of microglia are comprehensively regulated in humans.
Through their investigations, new knowledge emerged about the SPI1 gene, already known to scientists, as a factor that regulates a network of transcription factors and genes genetically linked to Alzheimer’s disease.
The team’s data may also be important in deciphering the molecular and genetic puzzles behind other neurodegenerative diseases in which microglia play a role, including Parkinson’s disease, multiple sclerosis and amyotrophic lateral sclerosis.
Dr. Roussos acknowledges that there is still much work for his team to understand how specific genes contribute to the development and growth of Alzheimer’s disease, and how new treatments can be developed.
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