Zeng Yanfang, Du Wenying, Zhang Mingkai, Walker Ariel, Han Ying, Ding Yuchuan
Department of Neurology, Xuanwu Hospital of Capital Medical University, No. 45 Changchun Street, Xicheng District, Beijing 100053, China.
Department of Neurology, Beijing Luhe Hospital of Capital Medical University, Beijing 101100, China.
Brain Sci. 2024 Mar 15;14(3):281. doi: 10.3390/brainsci14030281.
To explore the association between the apolipoprotein E (APOE) genotype and objectively assessed cognitive function.
In this cross-sectional study, 537 participants underwent a neuropsychological assessment for cognitive function and blood testing for APOE genotype. Based on cognitive test results, participants were stratified into two cohorts: Cognitively Unimpaired participants (CU) and Cognitively Impaired participants (CI). The CI group was further divided into Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD). Furthermore, we conducted age stratification, categorizing participants into three age groups: age 1: <65 years, age 2: 65-75 years, and age 3: >75 years. We assessed the disparities in cognitive function associated with ε4 carrier status across different age brackets. Plasma amyloid-β levels were measured in a cohort of 294 participants to investigate potential interactions involving ε4 carrier status, diagnosis, sex, or plasma markers.
The APOE genotypic distribution among the 537 participants was characterized as follows: ε2/ε2 (5 participants), ε2/ε3 (67), ε2/ε4 (13), ε3/ε3 (330), ε3/ε4 (113), and ε4/ε4 (9). Allele frequencies were: ε3 at 78.21%, ε4 at 13.41%, and ε2 at 8.38%. Notably, the ε4 carrier frequency was markedly elevated in the AD group at 81.8% when compared to MCI at 32.8% and CU at 21.3% ( < 0.05). Within the Cognitively Unimpaired (CU) cohort, the sole discernible contrast between ε4+ and ε4- emerged in STT-B ( < 0.05). Within the CI group, ε4 carriers showed statistically poorer scores as compared to non-ε4 carriers in several cognitive tests ( < 0.05). Age stratification result revealed that, among ε4 carriers, cognitive function scores within the age 3 group were significantly inferior to those of age 1 and age 2 groups ( < 0.05). Plasma amyloid-β detection was applied to the 294 participants. We tested plasma amyloid-β (Aβ42) and plasma amyloid-β (Aβ40) levels and calculated the Aβ42/Aβ40 ratio. We found that among female ε4 carriers, both Aβ42 and the Aβ42/Aβ40 ratio were notably lower than their male counterparts ( < 0.05).
The ε3/ε3 was the most prevalent among participants, succeeded by ε3/ε4 and ε2/ε3. The least prevalent were ε2/ε4, ε4/ε4, and ε2/ε2 genotypes. The ε3 was predominant, followed by the ε4 and ε2. Individuals with the ε4 allele exhibited significant cognitive impairment, with an especially high prevalence in AD group at 81.8%. The study unveils a pronounced correlation between the ε4 allele and cognitive deficits, implying its potential role in the advancement and severity of cognitive disorders, notably Alzheimer's disease. Cognitive function declines with age in individuals carrying the ε4, and women are more affected by ε4.
探讨载脂蛋白E（APOE）基因与客观评估的认知功能之间的关联。
在这项横断面研究中，537名参与者接受了认知功能的神经心理学评估以及APOE基因分型的血液检测。根据认知测试结果，参与者被分为两个队列：认知未受损参与者（CU）和认知受损参与者（CI）。CI组进一步分为轻度认知障碍（MCI）和阿尔茨海默病（AD）。此外，我们进行了年龄分层，将参与者分为三个年龄组：年龄1：<65岁，年龄2：65 - 75岁，年龄3：>75岁。我们评估了不同年龄组中与ε4携带者状态相关的认知功能差异。在294名参与者的队列中测量了血浆淀粉样蛋白β水平，以研究涉及ε4携带者状态、诊断、性别或血浆标志物的潜在相互作用。
537名参与者的APOE基因分型分布如下：ε2/ε2（5名参与者），ε2/ε3（67名），ε2/ε4（13名），ε3/ε3（330名），ε3/ε4（113名），和ε4/ε4（9名）。等位基因频率分别为：ε3占78.21%，ε4占13.41%，ε2占8.38%。值得注意的是，AD组中ε4携带者频率显著升高，为81.8%，而MCI组为32.8%，CU组为21.3%（<0.05）。在认知未受损（CU）队列中，ε4+和ε4-之间唯一可辨别的差异出现在STT-B中（<0.05）。在CI组中，在几项认知测试中，ε4携带者的得分在统计学上低于非ε4携带者（<0.05）。年龄分层结果显示，在ε4携带者中，年龄3组的认知功能得分显著低于年龄1组和年龄2组（<0.05）。对294名参与者进行了血浆淀粉样蛋白β检测。我们检测了血浆淀粉样蛋白β（Aβ42）和血浆淀粉样蛋白β（Aβ40）水平，并计算了Aβ42/Aβ40比值。我们发现，在女性ε4携带者中，Aβ42和Aβ42/Aβ40比值均显著低于男性（<0.05）。
ε3/ε3在参与者中最为普遍，其次是ε3/ε4和ε2/ε3。最不常见的是ε2/ε4、ε4/ε4和ε2/ε2基因型。ε3占主导地位，其次是ε4和ε2。携带ε4等位基因的个体表现出明显的认知障碍，在AD组中的患病率尤其高，为81.8%。该研究揭示了ε4等位基因与认知缺陷之间的显著相关性，暗示其在认知障碍尤其是阿尔茨海默病的进展和严重程度中的潜在作用。携带ε4的个体认知功能随年龄下降，且女性受ε4影响更大。
