Variants in MS4A4A Gene Influence Levels of Soluble TREM2 and Affect Susceptibility to Alzheimer’s Disease; Results Suggest Increased Focus on Brain’s Immune Cells (Microglia)

An international team of researchers led by scientists at Washington University School of Medicine in St. Louis has identified a pair of genes that influence risk for both late-onset and early-onset Alzheimer's disease. Most genes implicated thus far in Alzheimer's affect neurons that transmit messages, allowing different regions of the brain to communicate with one another. But the newly identified genes affect an entirely different population of cells: the brain's immune cells. The findings, published online on August 14, 2019 in Science Translational Medicine, could provide scientists with new targets and a strategy for delaying the onset of Alzheimer's symptoms. The article is titled “The MS4A Gene Cluster Is a Key Modulator of Soluble TREM2 and Alzheimer’s Disease Risk.” The identified genes -- known as MS4A4A and TREM2 -- operate in the microglia (image), the brain's immune cells. The genes influence Alzheimer's risk by altering levels of TREM2, a protein that is believed to help microglia cells clear excessive amounts of the Alzheimer's proteins beta-amyloid and tau from the brain. "The findings point to a new therapeutic strategy," said co-senior investigator Carlos Cruchaga, PhD, a Professor of Psychiatry and Director of the NeuroGenomics and Informatics Group at Washington University School of Medicine. "If we can do something to raise levels of the TREM2 protein in the cerebrospinal fluid, we may be able to protect against Alzheimer's disease or slow its development." In this study, the researchers measured soluble TREM2 levels in the cerebrospinal fluid of 813 older adults, most of whom were ages 55 to 90. Of those subjects, 172 had Alzheimer's disease, 169 were cognitively normal, and another 183 had early mild cognitive impairment.
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