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Abstract

Modern environmental improvements have extended average lifespan, leading to increased prevalence of neurodegenerative diseases such as dementia. While memory decline is a natural physiological process of aging, numerous studies have demonstrated that certain genotypes increase the risk of cognitive decline and dementia. The apolipoprotein E (APOE) ε4 allele is a well-established risk factor for Alzheimer’s disease (AD), the primary cause of dementia. APOE ε4 carriers not only have significantly elevated AD risk but also exhibit poorer cognitive performance and episodic memory decline. However, APOE ε4 alone inadequately predicts AD; its predictive power is limited by incomplete penetrance and polygenic interactions. Genome-wide association studies identify guanine nucleotide-binding protein beta polypeptide 3 (GNB3), a G-protein β subunit hub in APOE ε4-specific co-expression networks, but evidence linking GNB3 C825T to cognition or its interaction with APOE ε4 remains absent. In this study, we genotyped APOE and GNB3 C825T (rs5443) in 369 cognitively healthy adults at a healthy aging exhibition in Taiwan and assessed short-term memory performance. APOE ε4 carriers showed poorer short-term memory performance compared with non-carriers. While GNB3 genotype alone was not associated with memory performance, subgroup analyses suggested a trend toward poorer performance among APOE ε4 carriers with the GNB3 T allele (OR = 2.08, p = 0.08). However, formal interaction analysis did not demonstrate a statistically significant interaction effect. These findings suggest a potential association between APOE ε4 and short-term memory performance and indicate that GNB3 genotype may influence this relationship.

Keywords APOE, GNB3, Short-term memory

除了年齡，遺傳基因也可能影響記憶力。APOE ε4 是阿茲海默症最重要的遺傳風險因子，而 GNB3 基因參與腦神經訊號傳遞。本研究招募認知功能正常成年人（平均 52 歲），分析 APOE 與 GNB3（rs5443）基因型，並評估短期記憶表現。結果顯示，在調整年齡與性別後，APOE ε4 帶因者記憶測驗答錯 2 題以上的風險約為非帶因者的 2.2 倍。GNB3 基因型本身與記憶表現無顯著相關，但 APOE ε4 帶因者若同時攜帶 GNB3 T (C/T,T/T)對偶基因，短期記憶測驗表現較差。此結果顯示 GNB3 可能調節 APOE ε4 對記憶的影響，可作為日後探討失智風險基因交互作用的基礎證據，未來仍需更大規模、長期追蹤研究加以驗證。

全文連結: https://www.nature.com/articles/s41598-026-63878-1