Early reviews identified over 20 risk factors associated with Alzheimer's disease (AD) including age, familial inheritance, exposure to aluminium, traumatic brain injury (TBI), and associated co-morbidities such as vascular disease and infection. In the light of recent evidence, this review reconsiders these risk factors, identifies those currently regarded as important, and discusses various hypotheses to explain how they may cause AD. Rare forms of early-onset familial AD (EO-FAD) are strongly linked to causal gene mutations, viz. mutations in amyloid precursor protein (APP) and presenilin (PSEN1/2) genes. By contrast, late-onset sporadic AD (LO-SAD) is a multifactorial disorder in which age-related changes, genetic risk factors, such as allelic variation in apolipoprotein E (Apo E) and many other genes, vascular disease, TBI and risk factors associated with diet, the immune system, mitochondrial function, metal exposure, and infection are all implicated. These risk factors may act collectively to cause AD pathology: 1) by promoting the liberation of oxygen free radicals with age, 2) via environmental stress acting on regulatory genes early and later in life ('dual hit' hypothesis), or 3) by increasing the cumulative 'allostatic load' on the body over a lifetime. As a consequence, life-style changes which reduce the impact of these factors may be necessary to lower the risk of AD.

中文翻译：

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阿尔茨海默氏病的危险因素。

早期审查确定了与阿尔茨海默氏病（AD）相关的20多种危险因素，包括年龄，家族遗传，铝暴露，脑外伤（TBI）以及相关的合并症，例如血管疾病和感染。根据最近的证据，本次审查重新考虑了这些风险因素，确定了目前被认为重要的风险因素，并讨论了各种假设以解释它们可能如何引起AD。罕见的早期家族性AD（EO-FAD）形式与因果基因突变密切相关，即。淀粉样蛋白前体蛋白（APP）和早老素（PSEN1 / 2）基因的突变。相比之下，迟发性散发性AD（LO-SAD）是一种多因素疾病，其中年龄相关的变化，遗传危险因素，例如载脂蛋白E（Apo E）和许多其他基因的等位基因变异，血管疾病，TBI和与饮食，免疫系统，线粒体功能，金属暴露和感染相关的危险因素均涉及。这些风险因素可能共同导致AD病理：1）随着年龄的增长促进氧自由基的释放； 2）通过在生命的早期和晚期作用于调节基因的环境压力（“双重打击”假设）；或3）通过在一生中增加身体上的累积“ allostatic负荷”。结果，减少这些因素影响的生活方式改变可能是降低AD风险的必要条件。2）通过在生命的早期和晚期作用于调节基因的环境压力（“双重打击”假设），或3）通过增加一生中体内的累积“恒流负荷”来实现。结果，减少这些因素影响的生活方式改变可能是降低AD风险的必要条件。2）通过在生命的早期和晚期作用于调节基因的环境压力（“双重打击”假设），或3）通过增加一生中体内的累积“恒流负荷”来实现。结果，减少这些因素影响的生活方式改变可能是降低AD风险的必要条件。