Abstract:
A growing research body supports the connection between neurodegenerative disorders, including Alzheimer\'s disease (AD), and traffic-related air pollution (TRAP). However, the underlying mechanisms are not well understood. A deeper investigation of TRAP effects on hippocampal volume (HV), a major biomarker of neurodegeneration, may help clarify these mechanisms. Here, we explored TRAP associations with the HV in older participants of the UK Biobank (UKB), taking into account the presence of APOE e4 allele (APOE4), the strongest genetic risk factor for AD. Exposure to TRAP was approximated by the distance of the participant\'s main residence to the nearest major road (DNMR). The left/right HV was measured by magnetic resonance imaging (MRI) in cubic millimeters (mm3). Analysis of variance (ANOVA), Welch test, and regression were used to examine statistical significance. We found significant interactions between DNMR and APOE4 that influenced HV. Specifically, DNMR <50m (equivalent of a chronically high exposure to TRAP), and carrying APOE4 were synergistically associated with a significant (P = 0.01) reduction in the right HV by about 2.5% in women aged 60-75 years (results for men didn\'t reach a statistical significance). Results of our study suggest that TRAP and APOE4 jointly promote neurodegeneration in women. Living farther from major roads may help reduce the risks of neurodegenerative disorders, including AD, in female APOE4 carriers.
摘要:
越来越多的研究机构支持神经退行性疾病之间的联系,包括阿尔茨海默病(AD),与交通相关的空气污染(TRAP)。然而,潜在的机制还没有得到很好的理解。对TRAP对海马体积(HV)的影响进行了更深入的研究,神经变性的主要生物标志物,可能有助于澄清这些机制。这里,我们在英国生物库(UKB)的老年参与者中探索了TRAP与HV的关联,考虑到APOEe4等位基因(APOE4)的存在,AD最强的遗传危险因素。暴露于TRAP的近似值是参与者的主要住所到最近的主要道路(DNMR)的距离。通过磁共振成像(MRI)测量左/右HV,单位为立方毫米(mm3)。方差分析(ANOVA),韦尔奇试验,和回归用于检验统计学意义。我们发现DNMR和APOE4之间的显着相互作用影响HV。具体来说,DNMR<50m(相当于长期高暴露于TRAP),在60-75岁的女性中,携带APOE4与右HV显着降低约2.5%(P=0.01)协同相关(男性结果未达到统计学意义)。我们的研究结果表明,TRAP和APOE4共同促进了女性的神经变性。居住在远离主要道路的地方可能有助于降低神经退行性疾病的风险,包括AD,女性APOE4携带者。