DGIST (President Yang Kook) announced on the 15th that a research team led by Professor Jin-Soo Seo of the Department of Brain and Cognitive Sciences has identified the way in which astrocytes with ‘APOE4’, a genetic risk factor for Alzheimer’s dementia, cause pathological phenomena.
The APOE4 gene of astrocytes in the central nervous system is one of the genetic risk factors for Alzheimer’s dementia. In general, it is known that the risk of developing Alzheimer’s dementia is 5 to 10 times higher than that of those with the APOE3 genotype. However, it is not clear how the APOE4 gene causes pathological phenomena.
The research team produced brain cells with the APOE4 genotype and the control APOE3 genotype by applying the gene scissors technology that cuts DNA to human-derived pluripotent stem cells. We also explored the role of APOE4-star glial cells on amyloid beta production in neurons.
As a result of the study, a mechanism was found that, as APOE4 star glial cells secreted excessive cholesterol, increased the formation of lipid rafts in the neuronal cell membrane, leading to an increase in neuronal amyloid beta secretion.
In collaboration with the research team of Professor Dae-Won Moon, chair professor in the Department of New Biology, the research team used cell membrane analysis technology using time-of-flight secondary ion mass spectrometry (ToF-SIMS) to directly observe changes in cholesterol in lipid rafts of neurons.
Professor Seo Jin-soo said, “Through this study, the APOE4 genotype and astrocytes contributed to the amyloid beta production of neurons, suggesting a new direction for Alzheimer’s dementia research. We look forward to being able to present it,” he said.
The research team is currently analyzing the location of cell membrane proteins in lipid rafts by combining cell membrane analysis technology and protein staining technology. Through this study, it is expected to more accurately understand the cause of the promotion of amyloid beta production in Alzheimer’s dementia and to derive a method to effectively control it.
In this study, Se-in Lee, a Ph.D. student in the Department of Brain and Cognitive Sciences at DGIST, participated as the first author, and a research team led by Professor Dae-won Moon, Chair Professor of New Biology, participated as a co-researcher. The results were published online on the 26th of last month in the international academic journal Stem Cell Reports.
This research was carried out with support from the National Research Foundation of Korea’s Sejong Science Fellowship, Young and Senior Researcher Project, Brain Science Source Technology Development Project, and POSCO TJ Park Science Fellowship.
![An illustration of the pathogenesis of Alzheimer's disease using human pluripotent stem cells. Among the substances secreted by APOE4 star glial cells in the human body, an excessive amount of cholesterol is included. It is transmitted to the surrounding neurons and promotes the formation of cell membrane lipid rafts. Expansion of the lipid raft increases the cell membrane expression of amyloid proprotein and promotes the production of amyloid beta. [사진=DGIST]](https://i0.wp.com/cdn.hellodd.com/news/photo/202109/94299_307780_1915.jpg?w=800&ssl=1)
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