Institute of Physical Education, Health and Leisure Studies, National Cheng Kung University, Taiwan.
Department of Psychology, University of Pittsburgh, USA; Discipline of Exercise Science, College of Science, Health, Engineering and Education, Murdoch University, Western Australia.
Physiol Behav. 2021 Mar 1;230:113268. doi: 10.1016/j.physbeh.2020.113268. Epub 2020 Dec 28.
The present study examined whether the ɛ4 allele of the apolipoprotein E (ApoE) gene impacts molecular biomarkers and neurocognitive performance among individuals at genetic risk for developing Alzheimer's disease (AD). The correlations between physical fitness and molecular/neurocognitive indices were also explored.
Fasting blood samples were collected from 162 individuals with a family history of AD (ADFH). There were twenty-two carriers of the ApoE-4 variant (ApoE-4 group). For comparison purposes we randomly selected 22 non-ɛ4 carriers (non-ApoE-4 group) from the ADFH individuals. Circulating inflammatory cytokines (e.g., TNF-α, IL-1β, IL-6, IL-8, and IL-15), neuroprotective growth factors (e.g., BDNF, IGF-1, IGF-2, VEGF, and FGF-2), and Amyloid-β peptides (e.g., Aβ1-40 and Aβ1-42), neurocognitive performance [e.g., behavior and brain even-related potentials (ERP)] during a task-switching paradigm, as well as physical fitness scores were measured.
The ApoE-4 group relative to the non-ApoE-4 group was similar with respect to molecular biomarkers, physical fitness, and most measures of neurocognitive performance. However, ADFH individuals that were ɛ4 carriers exhibited significantly higher local switching accuracy costs, worse accuracy as well as smaller ERP P3 amplitudes for the memory-switching condition. Importantly, cardiorespiratory fitness levels were significantly correlated with accuracy for most task-switching conditions, and levels of BDNF, Aβ1-40, and Aβ1-42 collapsed across the two groups even when controlling for the age co-variable, while the ApoE-4 group revealed similar pattern of results.
These data suggest that individuals with ADFH that were carriers of the ApoE-4 variant performed worse on the task-switching paradigm and that this could be due to compromised task-set and memory updating processes. Physical exercise interventions aimed to enhance cardiorespiratory fitness levels could be a potential AD prevention strategy for ameliorating cognitive function and reducing the accumulation of the Aβ peptides in this high risk group.
本研究旨在探讨载脂蛋白 E（ApoE）基因的 ε4 等位基因是否会影响发生阿尔茨海默病（AD）遗传风险的个体的分子生物标志物和神经认知表现。还探讨了身体健康与分子/神经认知指标之间的相关性。
从有 AD 家族史的 162 名个体中采集空腹血样（ADFH）。有 22 名 ApoE-4 变体携带者（ApoE-4 组）。为了比较目的，我们从 ADFH 个体中随机选择了 22 名非 ε4 携带者（非 ApoE-4 组）。测量了循环炎症细胞因子（例如 TNF-α、IL-1β、IL-6、IL-8 和 IL-15）、神经保护生长因子（例如 BDNF、IGF-1、IGF-2、VEGF 和 FGF-2）和淀粉样β肽（例如 Aβ1-40 和 Aβ1-42）、认知表现[例如行为和大脑事件相关电位（ERP）]在任务切换范式期间，以及身体健康评分。
与非 ApoE-4 组相比，ApoE-4 组在分子生物标志物、身体健康和大多数神经认知表现方面相似。然而，携带 ApoE-4 的 ADFH 个体的局部切换准确性成本显著更高，准确性更差，记忆切换条件下的 ERP P3 幅度更小。重要的是，心肺健康水平与大多数任务切换条件的准确性显著相关，并且当控制年龄协变量时，BDNF、Aβ1-40 和 Aβ1-42 的水平在两组中都有相似的结果。
这些数据表明，携带 ApoE-4 变体的 ADFH 个体在任务切换范式上表现更差，这可能是由于任务集和记忆更新过程受损所致。旨在提高心肺健康水平的体育锻炼干预措施可能是改善认知功能和减少该高风险人群中 Aβ 肽积累的潜在 AD 预防策略。
