Institute of Public Health, National Yang-Ming University, Taipei, Taiwan.
Clinical and Translational Neuroscience Section, Laboratory of Behavioral Neuroscience, National Institute on Aging, Baltimore, MD, USA.
J Alzheimers Dis. 2020;75(2):417-427. doi: 10.3233/JAD-191335.
An epistatic interaction between the ɛ4 allele of apolipoprotein E (APOEɛ4) gene and the K-variant of butyrylcholinesterase (BCHE-K) genes has been previously reported to increase risk of Alzheimer's disease (AD). However, these observations were largely from case-control studies with small sample sizes.
To examine the interaction between APOEɛ4 and BCHE-K on: 1) the risk of incident AD and 2) rates of change in brain volumes and cognitive performance during the preclinical stages of AD in a prospective cohort study.
The study sample for survival analysis included 691 Caucasian participants (age at baseline, 58.4±9.9 years; follow-up time,16.9±9.7 years) from the Baltimore Longitudinal Study of Aging. The neuroimaging sample included 302 participants with 1,388 magnetic resonance imaging (MRI) scans. Cognitive performance was assessed in 703 participants over 4,908 visits.
A total of 122 diagnoses (79 AD, 43 mild cognitive impairment [MCI]) were identified. Participants with both APOEɛ4 and BCHE-K variants had a 3.7-fold greater risk of AD (Hazard ratio [HR] 95% CI=1.99-6.89, p < 0.001) compared to non-carriers of both genes (APOE ɛ4 x BCHE-K interaction p = 0.025). There was no APOE ɛ4-BCHE-K interaction effect on rate of cognitive decline and brain atrophy.
The APOE and BCHE genes interact to influence risk of incident AD/MCI but not rates of brain atrophy and decline in cognitive performance before onset of cognitive impairment. This may suggest the epistatic interaction between APOE ɛ4 and BCHE-K on AD risk is disease stage-dependent.
载脂蛋白 E（APOE）基因的ɛ4 等位基因与丁酰胆碱酯酶（BCHE）基因的 K 变体之间的上位性相互作用先前已被报道可增加阿尔茨海默病（AD）的风险。然而，这些观察结果主要来自于小样本量的病例对照研究。
在一项前瞻性队列研究中，检查 APOEɛ4 与 BCHE-K 之间的相互作用：1）AD 发病风险；2）AD 临床前阶段大脑体积和认知表现的变化率。
生存分析的研究样本包括来自巴尔的摩纵向老龄化研究的 691 名白种人参与者（基线年龄，58.4±9.9 岁；随访时间，16.9±9.7 年）。神经影像学样本包括 302 名参与者的 1388 次磁共振成像（MRI）扫描。在 4908 次就诊中评估了 703 名参与者的认知表现。
共确定了 122 例诊断（79 例 AD，43 例轻度认知障碍[MCI]）。与两个基因均非携带者相比，同时携带 APOEɛ4 和 BCHE-K 变体的参与者患 AD 的风险增加了 3.7 倍（风险比[HR]95%置信区间[CI]=1.99-6.89，p<0.001）（APOEɛ4 x BCHE-K 相互作用 p=0.025）。APOEɛ4-BCHE-K 相互作用对认知衰退和脑萎缩的速度没有影响。
APOE 和 BCHE 基因相互作用影响 AD/MCI 的发病风险，但不影响认知障碍发病前大脑萎缩和认知表现下降的速度。这可能表明 APOEɛ4 与 BCHE-K 之间的上位性相互作用与疾病阶段有关。
