Cacciottolo M, Wang X, Driscoll I, Woodward N, Saffari A, Reyes J, Serre M L, Vizuete W, Sioutas C, Morgan T E, Gatz M, Chui H C, Shumaker S A, Resnick S M, Espeland M A, Finch C E, Chen J C
Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA.
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Transl Psychiatry. 2017 Jan 31;7(1):e1022. doi: 10.1038/tp.2016.280.
Exposure to particulate matter (PM) in the ambient air and its interactions with APOE alleles may contribute to the acceleration of brain aging and the pathogenesis of Alzheimer's disease (AD). Neurodegenerative effects of particulate air pollutants were examined in a US-wide cohort of older women from the Women's Health Initiative Memory Study (WHIMS) and in experimental mouse models. Residing in places with fine PM exceeding EPA standards increased the risks for global cognitive decline and all-cause dementia respectively by 81 and 92%, with stronger adverse effects in APOE ɛ4/4 carriers. Female EFAD transgenic mice (5xFAD/human APOE ɛ3 or ɛ4) with 225 h exposure to urban nanosized PM (nPM) over 15 weeks showed increased cerebral β-amyloid by thioflavin S for fibrillary amyloid and by immunocytochemistry for Aβ deposits, both exacerbated by APOE ɛ4. Moreover, nPM exposure increased Aβ oligomers, caused selective atrophy of hippocampal CA1 neurites, and decreased the glutamate GluR1 subunit. Wildtype C57BL/6 female mice also showed nPM-induced CA1 atrophy and GluR1 decrease. In vitro nPM exposure of neuroblastoma cells (N2a-APP/swe) increased the pro-amyloidogenic processing of the amyloid precursor protein (APP). We suggest that airborne PM exposure promotes pathological brain aging in older women, with potentially a greater impact in ɛ4 carriers. The underlying mechanisms may involve increased cerebral Aβ production and selective changes in hippocampal CA1 neurons and glutamate receptor subunits.
暴露于环境空气中的颗粒物（PM）及其与载脂蛋白E（APOE）等位基因的相互作用可能会加速脑衰老并导致阿尔茨海默病（AD）的发病。在美国女性健康倡议记忆研究（WHIMS）的全年龄组老年女性队列以及实验小鼠模型中研究了颗粒空气污染物的神经退行性影响。居住在细颗粒物超过美国环境保护局（EPA）标准的地区分别使全球认知能力下降和全因痴呆的风险增加了81%和92%，对APOEɛ4/4携带者的不良影响更强。雌性早发性家族性AD转基因小鼠（5xFAD/人类APOEɛ3或ɛ4）在15周内暴露于城市纳米级颗粒物（nPM）225小时，通过硫黄素S检测纤维状淀粉样蛋白显示脑内β淀粉样蛋白增加，通过免疫细胞化学检测Aβ沉积物也增加，两者在APOEɛ4存在时均加剧。此外，nPM暴露增加了Aβ寡聚体，导致海马CA1神经突选择性萎缩，并降低了谷氨酸GluR1亚基。野生型C57BL/6雌性小鼠也表现出nPM诱导的CA1萎缩和GluR1减少。体外将神经母细胞瘤细胞（N2a-APP/swe）暴露于nPM会增加淀粉样前体蛋白（APP）的淀粉样生成前体加工。我们认为，暴露于空气中的PM会促进老年女性的病理性脑衰老，对ɛ4携带者的潜在影响可能更大。潜在机制可能涉及脑内Aβ生成增加以及海马CA1神经元和谷氨酸受体亚基的选择性变化。
