Alzheimer’s disease (AD) is an age related neurodegenerative disorder causing severe disability and important socio-economic burden, but with no cure available to date. To disentangle this puzzling disease genetic studies represented an important way for the comprehension of pathogenic mechanisms. Abnormal processing and accumulation of amyloid-β peptide (Aβ) has been considered the main cause and trigger factor of the disease. The amyloid cascade theory has fallen into crisis because the failure of several anti-amyloid drugs trials and because of the simple equation AD = abnormal Aβ deposition is not always the case. We now know that multiple neurodegenerative diseases share common pathogenic mechanisms leading to accumulation of misfolded protein species. Genome Wide Association studies (GWAS) led to the identification of large numbers of DNA common variants (SNPs) distributed on different chromosomes and modulating the Alzheimer’s risk. GWAS genes fall into several common pathways such as immune system and neuroinflammation, lipid metabolism, synaptic dysfunction and endocytosis, all of them addressing to novel routes for different pathogenic mechanisms. Other hints could be derived from epidemiological and experimental studies showing some lifestyles may have a major role in the pathogenesis of many age-associated diseases by modifying cell metabolism, proteostasis and microglia mediated neuroinflammation.

阿尔茨海默氏病（AD）是一种与年龄有关的神经退行性疾病，会导致严重的残疾和重要的社会经济负担，但迄今为止尚无治愈方法。弄清这种令人困惑的疾病，遗传学研究是理解致病机制的重要途径。淀粉样β肽（Aβ）的异常加工和积累被认为是该疾病的主要原因和触发因素。由于一些抗淀粉样蛋白药物试验的失败以及简单的方程AD =异常Aβ沉积并不总是这样，淀粉样蛋白级联理论已陷入危机。现在我们知道，多种神经退行性疾病具有共同的致病机制，导致错误折叠的蛋白质种类积聚。全基因组关联研究（GWAS）导致鉴定了分布在不同染色体上的大量DNA常见变异（SNP），并调节了阿尔茨海默氏症的风险。GWAS基因属于几种常见途径，例如免疫系统和神经炎症，脂质代谢，突触功能障碍和内吞作用，它们都针对不同的致病机制寻找新途径。从流行病学和实验研究中可以得出其他提示，表明某些生活方式可能通过改变细胞代谢，蛋白质稳态和小胶质细胞介导的神经炎症而在许多与年龄相关的疾病的发病机理中起主要作用。脂质代谢，突触功能障碍和胞吞作用，它们都针对不同的致病机制寻找新途径。从流行病学和实验研究中可以得出其他提示，表明某些生活方式可能通过改变细胞代谢，蛋白质稳态和小胶质细胞介导的神经炎症而在许多与年龄相关的疾病的发病机理中起主要作用。脂质代谢，突触功能障碍和胞吞作用，它们都针对不同的致病机制寻找新途径。从流行病学和实验研究中可以得出其他提示，表明某些生活方式可能通过改变细胞代谢，蛋白质稳态和小胶质细胞介导的神经炎症而在许多与年龄相关的疾病的发病机理中起主要作用。