[의학신문·일간보사=이승덕 기자]The mechanism of action on ApoE4, a risk factor for dementia, was identified by analyzing the brain tissue of a Korean patient with dementia.
The Korea Centers for Disease Control and Prevention (Chairman Eun-kyung Jeong) and the National Institute of Health (Chairman Jun-wook Kwon) announced on the 29th that they revealed a new pathological mechanism that aggravates Alzheimer’s dementia by ‘ApoE4’, known as a risk factor for dementia, through brain tissue analysis of dementia patients.
ApoE is a lipid and cholesterol carrier in the body, and there are three genotypes, E2, E3, and E4. Among them, it has been reported that people with the ApoE4 genotype increase the risk of dementia by 3-15 times, but the pathogenesis has not been clearly elucidated. .
The National Institutes of Health’s research team, Dr. Cheol-Man Cho and his team, revealed for the first time that ApoE4 inhibits FoxO3a, which is involved in autophagy, and causes the accumulation of phosphorylated tau protein found in the brain of dementia patients.
*Autophagy: A mechanism to decompose microorganisms, denatured proteins, and functionally problematic mitochondria that have invaded into cells and recycle them into amino acids and lipids necessary for cell growth. called mitophagy.
* Tau protein: It binds to and stabilizes microtubules constituting long axons in brain neurons. .
*Mitochondria: organelles within cells that use oxygen to produce energy (ATP) for cells.” src=”https://cdn.bosa.co.kr/news/photo/202109/2159152_190712_4749.png”/ >
*Autophagy: A mechanism to decompose microorganisms, denatured proteins, and functionally problematic mitochondria that have invaded into cells and recycle them into amino acids and lipids necessary for cell growth. called mitophagy.
* Tau protein: It binds to and stabilizes microtubules constituting long axons in brain neurons. .
*Mitochondria: Organelles within cells that use oxygen to produce energy (ATP) for cells.
In this study, for the first time, it was confirmed for the first time that FoxO3a was significantly reduced in the brain of dementia patients with the ApoE4 genotype, and autophagy-related proteins involved in the removal of mitochondria and proteins with functional problems were significantly reduced. .
Abnormal tau protein is usually removed by autophagy. In neurons with the ApoE4 genotype, it is interpreted that the autophagic function is greatly reduced and phosphorylated tau protein is accumulated. “This is the result of a study that well explains the pathology of an increase in damaged mitochondria in a patient’s brain neurons,” he said.
The results of this study are the results of analyzing the brain tissue of dementia patients in Korea collected through the Dementia Brain Banking project of the National Institute of Health. It was published in the latest issue of the Journal (first author: Hee-Young Son, Senior Researcher, Corresponding author: Cheol-Man Cho, Health Research Institute).
Koh Young-ho, head of the Brain Disease Research Division at the National Institute of Health, said, “The results of this study are expected to be an important scientific basis for the prevention and treatment of Alzheimer’s disease.”
