Cerebrospinal Fluid Biomarkers in Highly Exposed PM2.5 Urbanites: The Risk of Alzheimer's and Parkinson's Diseases in Young Mexico City Residents
Cerebrospinal Fluid Biomarkers in Highly Exposed PM2.5 Urbanites: The Risk of Alzheimer's and Parkinson's Diseases in Young Mexico City Residents
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DOI：
10.3233/jad-160472
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发表时间：
2016-01-01
影响因子：
4
通讯作者：
Lachmann, Ingolf
中科院分区：
文献类型：
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作者：
Calderon-Garciduenas, Lilian;Avila-Ramirez, Jose;Lachmann, Ingolf
暴露于高于美国环保局标准的细颗粒物（PM2.5）和臭氧（O-3）与阿尔茨海默病（AD）风险相关，而锰毒性则会诱导帕金森症。墨西哥城大都市区（MCMA）的儿童出生前和出生后持续高暴露于PM2.5，O-3，多环芳烃和金属。年轻的MCMA居民表现出额叶tau蛋白过度磷酸化和淀粉样蛋白β（A β）（1 - 42）弥漫性斑块，以及嗅觉神经和关键脑干核团中聚集和过度磷酸化的α-突触核蛋白。我们测量了来自MCMA和清洁空气对照的129个正常CSF样本中的总朊病毒蛋白（TPrP）、总tau（T-tau）、在苏氨酸181处磷酸化的tau（P-Tau）、A β（1 - 42）、α-突触核蛋白（t-alpha-syn和d-alpha-synuclein）、BDNF、胰岛素、瘦素和/或炎症介质。与对照组相比，MCMA儿童的A β（1 - 42）和BDNF浓度显著降低（分别为p = 0.005和0.02）。TPrP随累积PM2.5增加至5 μ g/m3，然后下降，与累积值或年龄无关（R-2 = 0.56）。在MCMA儿童中，TPrP与T-Tau和P-Tau强烈相关，而d-α-突触核蛋白显示与TNF α、IL 10和IL 6显著相关。总突触核蛋白在儿童时期与累积的PM2.5相关，随后在12岁后下降（R-2 = 0.47），而d-α-突触核蛋白表现出随累积的PM2.5增加的趋势（R-2 = 0.30）。CSF A β（1 - 42）、BDNF、α-突触核蛋白和TPrP变化在年轻的MCMA城市居民中不断发展，历史上表现出认知过程、气味识别缺陷、额叶细胞PrP下调以及神经病理性AD和PD标志的表现不佳。年轻MCMA居民的神经保护应该是公共卫生的优先事项。
Exposure to fine particulate matter (PM2.5) and ozone (O-3) above US EPA standards is associated with Alzheimer's disease (AD) risk, while Mn toxicity induces parkinsonism. Mexico City Metropolitan Area (MCMA) children have pre- and postnatal sustained and high exposures to PM2.5, O-3, polycyclic aromatic hydrocarbons, and metals. Young MCMA residents exhibit frontal tau hyperphosphorylation and amyloid-beta (A beta)(1-42) diffuse plaques, and aggregated and hyperphosphorylated alpha-synuclein in olfactory nerves and key brainstem nuclei. We measured total prion protein (TPrP), total tau (T-tau), tau phosphorylated at threonine 181 (P-Tau), A beta(1-42), alpha-synuclein (t-alpha-syn and d-alpha-synuclein), BDNF, insulin, leptin, and/or inflammatory mediators, in 129 normal CSF samples from MCMA and clean air controls. A beta(1-42) and BDNF concentrations were significantly lower in MCMA children versus controls (p = 0.005 and 0.02, respectively). TPrP increased with cumulative PM2.5 up to 5 mu g/m(3) and then decreased, regardless of cumulative value or age (R-2 = 0.56). TPrP strongly correlated with T-Tau and P-Tau, while d-alpha-synuclein showed a significant correlation with TNF alpha, IL10, and IL6 in MCMA children. Total synuclein showed an increment in childhood years related to cumulated PM2.5, followed by a decrease after age 12 years (R-2 = 0.47), while d-alpha-synuclein exhibited a tendency to increase with cumulated PM2.5 (R-2 = 0.30). CSF A beta(1-42), BDNF, alpha-synuclein, and TPrP changes are evolving in young MCMA urbanites historically showing underperformance in cognitive processes, odor identification deficits, downregulation of frontal cellular PrP, and neuropathological AD and PD hallmarks. Neuroprotection of young MCMA residents ought to be a public health priority.