A research team of Konkuk University Medical Center has found that people with apolipoprotein E epilepson4 (ApoE4) allele have a higher risk of developing Alzheimer's disease.

ApoE4 is one of the three alleles of ApoE2, ApoE3, and ApoE4 on chromosome 19. People with the allele have a four times higher risk of Alzheimer's disease and advanced onset.

A cohort study conducted in Canada has shown that the ApoE4 allele increased the prevalence of the cardiovascular and cerebrovascular disease, vascular dementia, Lewy body dementia in all races.

From left, Professors Moon Won-jin of the Department of Radiology and Moon Yeon-sil of the Department of Neurology at Konkuk University Medical Center, and Kim Hee-jin of the Department of Neurology at Hanyang Hospital Hospital.
From left, Professors Moon Won-jin of the Department of Radiology and Moon Yeon-sil of the Department of Neurology at Konkuk University Medical Center, and Kim Hee-jin of the Department of Neurology at Hanyang Hospital Hospital.

Although the ApoE4 allele is known to induce neuronal damage by inhibiting the amyloid-beta (Abeta) secretion, opinions have differed on its exact mechanism.

People with Alzheimer's disease have accumulated Abeta peptides in their brains. Abeta peptides have to cross the blood-brain barrier (BBB) to escape the brain.

The BBB maintains cranial nerve cells' function and selectively passes nutrients from the blood necessary to regulate the brain tissue's microenvironment and restricts toxic substances to protect brain cells. When the BBB collapses, the permeability changes, and the brain becomes vulnerable to various degenerative diseases, including Alzheimer's disease.

The research team, led by Professor Moon Won-jin, has confirmed higher permeability of the BBB in the hippocampus region responsible for memory than the group without ApoE4 with dynamic contrast enhancement imaging (DCE image) using a 3-Tesla magnetic resonance imaging scanner.

The researchers found that the BBB and brain atrophy's permeability in the hippocampus region are predictors of cognitive impairment even after correcting the age, education level, and genetic variation.

"The study results showed that the function of the BBB could vary, depending on the genotype, and the prognosis and drug response may also differ," Professor Moon said. "Impaired BBB function related to ApoE4 could be a new cause for degenerative brain diseases, including Alzheimer's disease."

Moon also pointed out that the BBB permeability observed in DCE images will play a role as an imaging phenotype of genetic mutations by measuring the effects of early mutations that could not be confirmed even with existing MRI and positron emission tomography images.

The study was conducted with the support of the Ministry of Health and Welfare's National Dementia Control Technology Development Project and the Korea Research Foundation's research project.

The Journal of Cerebral Blood Flow and Metabolism has recently published the study.

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