Alzheimer’s disease (AD), an aging-related neurodegenerative disease, is a major cause of dementia in the elderly. Although the early-onset (familial) AD is attributed to mutations in the genes coding for amyloid-β protein precursor (AβPP) and presenilin1/presenilin 2 (PS1/PS2), the cause for the late-onset AD (LOAD), which accounts for more than 95% of AD cases, remains unclear. Aging is the greatest risk factor for LOAD, whereas the apolipo protein E4 allele (APOEɛ4) is believed to be a major genetic risk factor in acquiring LOAD, with female APOE ɛ4 carriers at highest risk. Nonetheless, not all the elderly, even older female APOE ɛ4 carriers, develop LOAD, suggesting that other factors, including environmental exposure, must play a role. This review summarizes recent studies that show a potential role of environmental exposure, especially ozone and particulate matter exposure, in the development of AD. Interactions between environmental exposure, genetic risk factor (APOE ɛ4), and sex in AD pathophysiology are also discussed briefly. Identification of environmental risk factor(s) and elucidation of the complex interactions between genetic and environmental risk factors plus aging and female sex in the onset of AD will be a key to our understanding of the etiology and pathogenesis of AD and the development of the strategies for its prevention and treatment.

中文翻译：

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臭氧和颗粒物暴露与阿尔茨海默病：人类和动物研究综述。

阿尔茨海默病（AD）是一种与衰老相关的神经退行性疾病，是导致老年人痴呆的主要原因。尽管早发性（家族性）AD 归因于编码淀粉样蛋白前体 (AβPP) 和早老素 1/早老素 2 (PS1/PS2) 的基因突变，但晚发性 AD (LOAD) 的原因是占 AD 病例的 95% 以上，仍不清楚。衰老是 LOAD 的最大风险因素，而载脂蛋白 E4 等位基因 (APOEɛ4) 被认为是获得 LOAD 的主要遗传风险因素，女性 APOEɛ4 携带者的风险最高。尽管如此，并非所有老年人，甚至年长的女性 APOE ɛ4 携带者都会出现 LOAD，这表明包括环境暴露在内的其他因素必须发挥作用。这篇综述总结了最近的研究，这些研究显示了环境暴露的潜在作用，在 AD 的发展过程中，尤其是臭氧和颗粒物暴露。还简要讨论了 AD 病理生理学中环境暴露、遗传风险因素 (APOE ɛ4) 和性别之间的相互作用。识别环境风险因素并阐明遗传和环境风险因素以及衰老和女性在 AD 发病过程中的复杂相互作用将是我们理解 AD 的病因和发病机制以及制定策略的关键对其进行预防和治疗。