The University of Montana, Missoula, MT, 59812, USA; Universidad del Valle de México, 14370, Mexico.
Instituto Nacional de Pediatría, Mexico City, 04530, Mexico.
Environ Res. 2018 Oct;166:348-362. doi: 10.1016/j.envres.2018.06.027. Epub 2018 Jun 20.
There is growing evidence that air pollution is a risk factor for a number of neurodegenerative diseases, most notably Alzheimer's (AD) and Parkinson's (PD). It is generally assumed that the pathology of these diseases arises only later in life and commonly begins within olfactory eloquent pathways prior to the onset of the classical clinical symptoms. The present study demonstrates that chronic exposure to high levels of air pollution results in AD- and PD-related pathology within the olfactory bulbs of children and relatively young adults ages 11 months to 40 years. The olfactory bulbs (OBs) of 179 residents of highly polluted Metropolitan Mexico City (MMC) were evaluated for AD- and alpha-synuclein-related pathology. Even in toddlers, hyperphosphorylated tau (hTau) and Lewy neurites (LN) were identified in the OBs. By the second decade, 84% of the bulbs exhibited hTau (48/57), 68% LNs and vascular amyloid (39/57) and 36% (21/57) diffuse amyloid plaques. OB active endothelial phagocytosis of red blood cell fragments containing combustion-derived nanoparticles (CDNPs) and the neurovascular unit damage were associated with myelinated and unmyelinated axonal damage. OB hTau neurites were associated mostly with pretangle stages 1a and 1b in subjects ≤ 20 years of age, strongly suggesting olfactory deficits could potentially be an early guide of AD pretangle subcortical and cortical hTau. APOE4 versus APOE3 carriers were 6-13 times more likely to exhibit OB vascular amyloid, neuronal amyloid accumulation, alpha-synuclein aggregates, hTau neurofibrillary tangles, and neurites. Remarkably, APOE4 carriers were 4.57 times more likely than non-carriers to die by suicide. The present findings, along with previous data that over a third of clinically healthy MMC teens and young adults exhibit low scores on an odor identification test, support the concept that olfactory testing may aid in identifying young people at high risk for neurodegenerative diseases. Moreover, results strongly support early neuroprotective interventions in fine particulate matter (PM) and CDNP's exposed individuals ≤ 20 years of age, and the critical need for air pollution control.
越来越多的证据表明，空气污染是许多神经退行性疾病的风险因素，尤其是阿尔茨海默病（AD）和帕金森病（PD）。一般认为，这些疾病的病理学仅在生命后期出现，通常在经典临床症状出现之前就开始于嗅觉相关的通路中。本研究表明，儿童和相对年轻的成年人（11 个月至 40 岁）长期暴露于高水平的空气污染会导致嗅球中出现 AD 和 PD 相关的病理学。对高度污染的墨西哥城大都市区（MMC）的 179 名居民的嗅球进行了评估，以检测 AD 和α-突触核蛋白相关的病理学。即使在幼儿中，也可以在嗅球中识别出过度磷酸化的 tau（hTau）和路易小体（LN）。到第二个十年，84％的嗅球都表现出 hTau（48/57），68％的 LN 和血管淀粉样蛋白（39/57），36％（21/57）的弥漫性淀粉样斑块。嗅球中活性内皮细胞对含有燃烧衍生的纳米颗粒（CDNP）的红细胞碎片的吞噬作用以及神经血管单元的损伤与有髓和无髓轴突损伤有关。嗅球中的 hTau 神经突主要与≤20 岁的患者的预缠结阶段 1a 和 1b 相关，这强烈表明嗅觉缺陷可能是 AD 预缠结皮质下和皮质 hTau 的早期指标。APOE4 与 APOE3 携带者患嗅球血管淀粉样蛋白、神经元淀粉样蛋白堆积、α-突触核蛋白聚集体、hTau 神经原纤维缠结和神经突的风险高 6-13 倍。值得注意的是，APOE4 携带者自杀的可能性比非携带者高 4.57 倍。本研究结果以及先前的研究数据表明，超过三分之一的临床健康的 MMC 青少年和年轻人在嗅觉识别测试中得分较低，支持嗅觉测试可能有助于识别处于神经退行性疾病高风险的年轻人的观点。此外，研究结果还强烈支持对≤20 岁的 PM 和 CDNP 暴露个体进行早期神经保护干预，以及对空气污染控制的迫切需要。
