Domestic Researchers Uncover Interaction Mechanism Between Alzheimer's Causative Protein and High-Risk Genes

Alzheimer's Disease Causative Protein Deposits
Distinct Brain Functional Connectivity Activation Patterns According to Presence of High-Risk Genes

Professor Im Hyun-guk (left) from Yeouido St. Mary's Hospital Brain Health Center, Professor Kang Dong-gu from the Department of Psychiatry at Seoul St. Mary's Hospital.

[Asia Economy Reporter Lee Gwan-joo] Domestic researchers have uncovered the mutual pathological mechanism between the major risk factor for Alzheimer's disease, the 'ApoE4 (APOE4)' gene, and the degree of amyloid-beta protein deposition in cognitively normal individuals.

The research team led by Professor Lim Hyun-guk of the Brain Health Center at Yeouido St. Mary's Hospital, Catholic University, and Professor Kang Dong-woo of the Department of Psychiatry at Seoul St. Mary's Hospital announced on the 31st that after classifying the degree of beta-amyloid protein accumulation into below and above threshold groups, they confirmed that changes in brain function and cognition according to the degree of deposition significantly differed depending on the presence or absence of the ApoE4 (APOE4) gene.

Alzheimer's disease, a representative neurodegenerative disorder, involves the accumulation of amyloid-beta protein in the brain 10 to 15 years before symptom onset, which gradually induces changes in brain function and structure, as well as cognitive decline. Therefore, amyloid-beta protein deposition occurs even in cognitively normal states, marking a period that draws attention as it can increase the possibility of early diagnosis and treatment. Additionally, in sporadic Alzheimer's disease, which accounts for 99% of Alzheimer's cases, multiple factors influence the disease onset process. In particular, it is known that the presence or absence of the ApoE4 gene affects the severity of pathological progression and the risk of dementia onset.

The research team classified an elderly group (182 individuals) within the normal cognitive function range into a beta-amyloid protein positive group above the threshold (72 individuals) and a group below the threshold (110 individuals). They then evaluated the degree of beta-amyloid protein deposition, the functional connectivity of resting-state brain networks, and the presence or absence of the high-risk sporadic Alzheimer's disease gene, ApoE4. They also extracted major brain networks involved in cognitive changes and conducted analyses on intra-network and inter-network connectivity.

As a result, in individuals carrying the ApoE4 gene, the below-threshold amyloid-beta deposition group showed enhanced network connectivity in the precuneus and cerebellum crus, whereas the above-threshold deposition group exhibited weakened network connectivity in the insula. Although the patterns of network connectivity changes differed between the two groups carrying the ApoE4 gene, these changes in both groups were found to contribute to improvements in executive function and memory.

Professor Lim Hyun-guk stated, “Closely identifying the causes of brain function and clinical indicator changes at the earliest stage when amyloid-beta protein begins to deposit in the brain is essential to establish evidence for early dementia treatment.” He added, “This study is significant in that it evaluated the impact of below-threshold amyloid-beta protein deposition on brain function impairment compared to the above-threshold deposition group, considering interactions with high-risk genes.”

This study was published in Frontiers in Aging Neuroscience.

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