The mechanism of action of Apoe E4, a dementia risk factor, was identified by analyzing the brain tissue of Korean dementia patients.

ApoE is a lipid and cholesterol carrier in the body, and there are three genotypes of E2, E3, and E4, of which the risk of developing dementia has been reported to increase by 3-15 times, but the pathogenesis has not yet been clearly identified.

Recently, a team led by Dr. Cho Cheol-man of the Institute of Health revealed for the first time that ApoE4 inhibits FoxO3a, which is involved in autophagy, causing the accumulation of phosphorylated tau protein found in the brain of dementia patients.

The research method is as follows. 1) The research team analyzed the expression of genes controlled by FoxO3a and FoxO3a in 12 cases of brain tissues collected by the dementia brain bank of Seoul National University Hospital with protein immunoblotting. 2) The amount of each protein was quantified and the difference between the ApoE4 genotype holder and the non-possessor was statistically analyzed.

The research results are as follows. 1) The research team confirmed that in the case of ApoE4 genotype holders, the amount of FoxO3a was greatly reduced, and the inactivated form of FoxO3a was increased, so its activity was greatly suppressed. 2) As a result of investigating the expression of ATG12, beclin-1, BNIP3, and PINK1 proteins subject to FoxO3a expression control in ApoE4 genotype holders, it was confirmed that the level was reduced compared to non-possessors of ApoE4 genotype. 3) It was confirmed that the phosphorylated tau protein was increased, and the function of removing mitochondria, which has functional problems due to the reduction of phosphorylated ubiquitin and optineurin, was also hindered.

The results of this study are expected to be an important scientific basis for the development of the prevention and treatment of Alzheimer disease.

Categories: Clinical