As immune cells move throughout the brain, they act as the first line of defense against viruses, toxic substances, and damaged neurons, and rush to wipe them out.
Researchers at Indiana University School of Medicine are investigating how these immune cells function in the brain.Microglia-is connected with Genetic mutation Recently seen in patients with Alzheimer’s disease.They made their discovery today Science Advances..
The study was led by Dr. Hande Karahan, a postdoctoral fellow in medicine. Molecular genetics, And Jungsu Kim, Ph.D., Professor of Medicine and Molecular Genetics at P. Michael Conneally. Found that deletion of a gene called ABI3 significantly increased the accumulation of amyloid beta plaques in the brain and reduced the amount of microglia around the plaques. ..
“This study provides additional insights into understanding the key functions of microglia that contribute to disease and helps identify new therapeutic targets,” Karahan said. — A mutation in the ABI3 gene has been identified. Researchers have concluded that this mutation increases the risk of late-onset Alzheimer’s disease.
“But there was no research into the function of the ABI3 gene in the brain or how this gene affects the function of microglia,” said Karahan, a fact that led to her study. The team removed the ABI3 gene from Alzheimer’s disease. Mouse model We tested the function of genes in cell culture microglia. Mouse models showed elevated levels of plaque and inflammation in the brain, and signs of synaptic dysfunction. This is a feature associated with learning and memory loss of the disease.
In addition, Karahan said gene deletions impair the movement of microglia.Immunity cell You cannot approach the plaque and try to remove the protein. Amyloid plaques are common in the brains of patients with Alzheimer’s disease. Amyloid beta proteins aggregate to form amyloid plaques, breaking nerve cell connections.
“Our study provides the first in vivo functional evidence that loss of ABI3 function may increase the risk of developing Alzheimer’s disease by affecting amyloid beta accumulation and neuroinflammation.” Karahan said.
Over the past few years, Karahan has built on her research on Alzheimer’s disease. In 2019, Karahan was founded by the Indiana Alzheimer’s Disease Research Center and was funded by generous donations from James and Nancy Carpenter and matching donations from the Stark Neuroscience Institute, where Karahan is conducting research. I received a Saralauche Memorial Fellowship for my research.
Karahan and Kim received three separate grants to support the study from the National Institutes of Health (NIH), the National Institute on Aging, for the study of Alzheimer’s disease, with $ 7.8 million over the next five years. Brought.
“One grant will fund the creation of a mouse model that can remove the ABI3 gene from all cell types in the body, including microglia and peripherals in the brain. Immune cells“Once we’ve validated this new model, we’ll make it available to others in the research community for our research,” Kim said.
Other grants will fund additional mouse and cell models of the team to further investigate how the ABI3 gene in microglia affects the pathology of Alzheimer’s disease, as well as state-of-the-art technology including: To fund. brain Imaging using Bruker BioSpec 9.4TPET-MRI Scanner, Roberts Translational Imaging Facility, Stark Neurosciences Research Institute.
Each of these projects has the ultimate goal of identifying drug-discoverable targets for treatment. diseaseSaid Karahan and Kim. The team is working with the IU School of Medicine-Purdue TaRget Enablement to accelerate the development of treatments for Alzheimer’s disease (TREAT-AD) center.
Deletion of the Hande Karahan et al, Abi3 locus exacerbates the neuropathological features of Alzheimer’s disease in a mouse model of Aβ amyloidosis. Science Advances (2021). DOI: 10.1126 / sciadv.abe3954
Indiana University School of Medicine
Quote: Researchers have obtained brain immune cells from https://medicalxpress.com/news/2021-11-role-gene-alzheimer-disease-brain.html on November 6, 2021 (November 2021). 6th) Investigate the role of genes related to Alzheimer’s disease
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