BACKGROUND Increased exposure to ambient air pollution, especially fine particulate matter ≤2.5μm (PM2.5) is associated with poorer brain health and increased risk for Alzheimer's disease (AD) and related dementias. The locus coeruleus (LC), located in the brainstem, is one of the earliest regions affected by tau pathology seen in AD. Its diffuse projections throughout the brain include afferents to olfactory areas that are hypothesized conduits of cerebral particle deposition. Additionally, extensive contact of the LC with the cerebrovascular system may present an additional route of exposure to environmental toxicants. OBJECTIVE Our aim was to investigate if exposure to PM2.5 was associated with LC integrity in a nationwide sample of men in early old age, potentially representing one pathway through which air pollution can contribute to increased risk for AD dementia. METHODS We examined the relationship between PM2.5 and in vivo magnetic resonance imaging (MRI) estimates of LC structural integrity indexed by contrast to noise ratio (LCCNR) in 381 men [mean age=67.3; standard deviation (SD)=2.6] from the Vietnam Era Twin Study of Aging (VETSA). Exposure to PM2.5 was taken as a 3-year average over the most recent period for which data were available (average of 5.6 years prior to the MRI scan). We focused on LCCNR in the rostral-middle portion of LC due to its stronger associations with aging and AD than the caudal LC. Associations between PM2.5 exposures and LC integrity were tested using linear mixed effects models adjusted for age, scanner, education, household income, and interval between exposure and MRI. A co-twin control analysis was also performed to investigate whether associations remained after controlling for genetic confounding and rearing environment. RESULTS Multiple linear regressions revealed a significant association between PM2.5 and rostral-middle LCCNR (β=-0.16; p=0.02), whereby higher exposure to PM2.5 was associated with lower LCCNR. A co-twin control analysis found that, within monozygotic pairs, individuals with higher PM2.5 exposure showed lower LCCNR (β=-0.11; p=0.02), indicating associations were not driven by genetic or shared environmental confounds. There were no associations between PM2.5 and caudal LCCNR or hippocampal volume, suggesting a degree of specificity to the rostral-middle portion of the LC. DISCUSSION Given previous findings that loss of LC integrity is associated with increased accumulation of AD-related amyloid and tau pathology, impacts on LC integrity may represent a potential pathway through which exposure to air pollution increases AD risk. https://doi.org/10.1289/EHP14344.

中文翻译：

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越南时代双胞胎衰老研究 （VETSA） 中细颗粒物暴露与 MRI 评估的蓝斑完整性之间的关联。


背景 暴露于周围空气污染中，尤其是细颗粒物 ≤2.5μm （PM2.5） 的增加与大脑健康状况较差以及阿尔茨海默病 （AD） 和相关痴呆症的风险增加有关。位于脑干的蓝斑 （LC） 是 AD 中最早受 tau 病变影响的区域之一。它在整个大脑中的弥散投射包括对嗅觉区域的传入神经，这些嗅觉区域是假设的脑颗粒沉积的管道。此外，LC 与脑血管系统的广泛接触可能是另一种暴露于环境毒物的途径。目的 我们的目标是调查暴露于 PM2.5 是否与全国早期老年男性样本的 LC 完整性相关，这可能代表空气污染可能导致 AD 痴呆风险增加的一种途径。方法 我们检查了 PM2.5 与越南时代双胞胎衰老研究 （VETSA） 中 381 名男性 [平均年龄 = 67.3;标准差 （SD） = 2.6] 的 LC 结构完整性的体内磁共振成像 （MRI） 估计之间的关系。PM2.5 暴露量作为有数据的最近一段时间的 3 年平均值（MRI 扫描前的平均 5.6 年）。我们专注于 LC 喙部-中间部分的 LCCNR，因为它与衰老和 AD 的相关性比尾部 LC 更强。使用线性混合效应模型测试 PM2.5 暴露与 LC 完整性之间的关联，该模型针对年龄、扫描仪、教育程度、家庭收入以及暴露与 MRI 之间的间隔进行了调整。还进行了共双胞胎对照分析，以调查在控制遗传混杂和饲养环境后是否仍然存在关联。 结果 多元线性回归显示 PM2.5 与喙-中 LCCNR 之间存在显著相关性 （β=-0.16;p=0.02），其中较高的 PM2.5 暴露与较低的 LCCNR 相关。共同双胞胎对照分析发现，在同卵对中，PM2.5 暴露量较高的个体表现出较低的 LCCNR （β=-0.11;p=0.02），表明关联不是由遗传或共享环境混杂因素驱动的。PM2.5 与尾部 LCCNR 或海马体积之间没有关联，表明 LC 的喙部-中间部分具有一定程度的特异性。讨论鉴于先前的研究发现，液相色谱完整性的丧失与 AD 相关淀粉样蛋白和 tau 蛋白病理学的积累增加有关，对液相色谱完整性的影响可能代表了暴露于空气污染中增加 AD 风险的潜在途径。https://doi.org/10.1289/EHP14344。