From the Department of Epidemiology (G.M.C., D.L., S.E., A.H.), Gangarosa Department of Environmental Health (Z.L., D.L., S.E., A.H.), Rollins School of Public Health, and Department of Pathology and Laboratory Medicine (M.G.), Emory University; Department of Neurology (M.G., A.I.L., J.J.L., T.W.), Emory University School of Medicine, Atlanta; Division of Mental Health (A.W.), Atlanta VA Medical Center, Decatur; Department of Psychiatry (A.W.), Emory University School of Medicine; and Department of Human Genetics (T.W.), Emory University, Atlanta, GA.
Neurology. 2024 Mar 12;102(5):e209162. doi: 10.1212/WNL.0000000000209162. Epub 2024 Feb 21.
BACKGROUND AND OBJECTIVES: Fine particulate matter (PM) exposure has been found to be associated with Alzheimer disease (AD) and is hypothesized to cause inflammation and oxidative stress in the brain, contributing to neuropathology. The gene, a major genetic risk factor of AD, has been hypothesized to modify the association between PM and AD. However, little prior research exists to support these hypotheses. This study investigates the association between traffic-related PM and AD hallmark pathology, including effect modification by genotype, in an autopsy cohort. METHODS: A cross-sectional study was conducted using brain tissue donors enrolled in the Emory Goizueta AD Research Center who died before 2020 (n = 224). Donors were assessed for AD pathology including the Braak stage, Consortium to Establish a Registry for AD (CERAD) score, and combined AD neuropathologic change (ABC) score. Traffic-related PM concentrations were modeled for the metro-Atlanta area during 2002-2019 with a spatial resolution of 200-250 m. One-year, 3-year, and 5-year average PM concentrations before death were matched to participants' home address. We assessed the association between traffic-related PM and AD hallmark pathology and effect modification by genotype, using adjusted ordinal logistic regression models. RESULTS: Among the 224 participants, the mean age of death was 76 years, and 57% had at least 1 ε4 copy. Traffic-related PM was significantly associated with the CERAD score for the 1-year exposure window (odds ratio [OR] 1.92; 95% CI 1.12-3.30) and the 3-year exposure window (OR 1.87; 95% CI 1.01-3.17). PM was also associated with higher Braak stage and ABC score albeit nonsignificantly. The strongest associations between PM and neuropathology markers were among those without ε4 alleles (e.g., for the CERAD score and 1-year exposure window, OR 2.31; 95% CI 1.36-3.94), though interaction between PM and genotype was not statistically significant. DISCUSSION: Our study found traffic-related PM exposure was associated with the CERAD score in an autopsy cohort, contributing to epidemiologic evidence that PM affects β-amyloid deposition in the brain. This association was particularly strong among donors without ε4 alleles. Future studies should further investigate the biological mechanisms behind this association.
背景与目的：细颗粒物（PM）暴露与阿尔茨海默病（AD）有关，据推测它会在大脑中引起炎症和氧化应激，从而导致神经病理学变化。 基因是 AD 的主要遗传风险因素，据推测它可以改变 PM 与 AD 之间的关联。然而，之前的研究很少支持这些假设。本研究在尸检队列中调查了与交通相关的 PM 与 AD 标志性病理学之间的关联，包括 基因型对其的影响修饰。
方法：本研究采用病例对照研究，使用参加埃默里·戈伊祖塔 AD 研究中心的脑组织供体进行，这些供体在 2020 年之前死亡（n=224）。对供体进行 AD 病理学评估，包括 Braak 分期、AD 研究中心（CERAD）评分和联合 AD 神经病理学变化（ABC）评分。使用空间分辨率为 200-250 米的模型，对 2002-2019 年亚特兰大地区的交通相关 PM 浓度进行建模。在死亡前一年、三年和五年的平均 PM 浓度与参与者的家庭住址相匹配。我们使用调整后的有序逻辑回归模型评估了交通相关 PM 与 AD 标志性病理学之间的关联，以及 基因型的修饰作用。
结果：在 224 名参与者中，死亡时的平均年龄为 76 岁，57%的参与者至少有 1 个 ε4 拷贝。交通相关 PM 与 1 年暴露窗（比值比 [OR] 1.92；95%置信区间 [CI] 1.12-3.30）和 3 年暴露窗（OR 1.87；95% CI 1.01-3.17）的 CERAD 评分显著相关。PM 还与更高的 Braak 分期和 ABC 评分相关，但无统计学意义。PM 与神经病理学标志物之间最强的关联存在于没有 ε4 等位基因的个体中（例如，对于 CERAD 评分和 1 年暴露窗，OR 2.31；95% CI 1.36-3.94），尽管 PM 与 基因型之间的交互作用无统计学意义。
讨论：本研究在尸检队列中发现交通相关的 PM 暴露与 CERAD 评分有关，这为 PM 影响大脑中 β-淀粉样蛋白沉积的流行病学证据提供了支持。这种关联在没有 ε4 等位基因的供体中尤为明显。未来的研究应进一步探讨这种关联背后的生物学机制。
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