The University of Montana, Missoula, MT 59812, USA; Universidad del Valle de México, 14370, Mexico.
Instituto Nacional de Pediatría, 04530, Mexico.
Environ Res. 2018 Jul;164:475-487. doi: 10.1016/j.envres.2018.03.023. Epub 2018 Mar 26.
Exposures to fine particulate matter (PM) and ozone (O) above USEPA standards are associated with Alzheimer's disease (AD) risk. Metropolitan Mexico City (MMC) residents have life time exposures to PM and O above USEPA standards. We investigated AD intra and extracellular protein aggregates and ultrastructural neurovascular pathology in 203 MMC residents age 25.36 ± 9.23 y. Immunohistochemical methods were used to identify AT8 hyperphosphorilated tau (Htau) and 4G8 (amyloid β 17-24). Primary outcomes: staging of Htau and amyloid, per decade and cumulative PM (CPM) above standard. Apolipoprotein E allele 4 (APOE4), age and cause of death were secondary outcomes. Subcortical pretangle stage b was identified in an 11month old baby. Cortical tau pre-tangles, neurofibrillary tangles (NFT) Stages I-II, amyloid phases 1-2, Htau in substantia nigrae, auditory, oculomotor, trigeminal and autonomic systems were identified by the 2nd decade. Progression to NFT stages III-V was present in 24.8% of 30-40 y old subjects. APOE4 carriers have 4.92 times higher suicide odds (p = 0.0006), and 23.6 times higher odds of NFT V (p < 0.0001) v APOE4 non-carriers having similar CPM exposure and age. Age (p = 0.0062) and CPM (p = 0.0178) were significant for developing NFT V. Combustion-derived nanoparticles were associated with early and progressive damage to the neurovascular unit. Alzheimer's disease starting in the brainstem of young children and affecting 99.5% of young urbanites is a serious health crisis. Air pollution control should be prioritised. Childhood relentless Htau makes a fundamental target for neuroprotective interventions and the first two decades are critical. We recommend the concept of preclinical AD be revised and emphasize the need to define paediatric environmental, nutritional, metabolic and genetic risk factor interactions of paramount importance to prevent AD. AD evolving from childhood is threating the wellbeing of our children and future generations.
暴露于美国环保署标准以上的细颗粒物 (PM) 和臭氧 (O) 与阿尔茨海默病 (AD) 风险有关。墨西哥大都市 (MMC) 的居民一生都暴露于高于美国环保署标准的 PM 和 O 中。我们研究了 203 名年龄在 25.36±9.23 岁的 MMC 居民的 AD 细胞内和细胞外蛋白聚集体以及超微结构神经血管病理学。使用免疫组织化学方法来识别 AT8 过度磷酸化的 tau (Htau) 和 4G8 (淀粉样 β 17-24)。主要结果：每十年和累积 PM (CPM) 超过标准对 Htau 和淀粉样蛋白进行分期。载脂蛋白 E 等位基因 4 (APOE4)、年龄和死因是次要结果。在一个 11 个月大的婴儿中发现了皮质下预缠结 b 期。在第二个十年中，识别出皮质 tau 预缠结、神经纤维缠结 (NFT) I-II 期、淀粉样蛋白相 1-2、黑质中的 Htau、听觉、动眼、三叉神经和自主神经系统。在 30-40 岁的受试者中，有 24.8%进展到 NFT III-V 期。APOE4 携带者自杀的几率高出 4.92 倍 (p=0.0006)，NFT V 的几率高出 23.6 倍 (p<0.0001)，而 APOE4 非携带者的 CPM 暴露和年龄相似。年龄 (p=0.0062) 和 CPM (p=0.0178) 对 NFT V 的发展有显著影响。源自燃烧的纳米颗粒与神经血管单元的早期和进行性损伤有关。从幼儿期开始并影响 99.5%的城市年轻人的阿尔茨海默病是一个严重的健康危机。应优先控制空气污染。儿童时期持续的 Htau 是神经保护干预的基本靶点，前二十年至关重要。我们建议修订临床前 AD 的概念，并强调需要定义儿科环境、营养、代谢和遗传危险因素的相互作用，这对预防 AD 至关重要。从儿童期开始发展的 AD 正在威胁我们孩子和后代的健康。
