Laboratorio de Patogénesis Molecular, Laboratorio 4, Edificio A4, Carrera Médico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla 54090, Edomex, Mexico.
Departamento de Neurobiología del Desarrollo y Neurofisiología, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Juriquilla 76230, Querétaro, Mexico.
Int J Mol Sci. 2023 Feb 13;24(4):3754. doi: 10.3390/ijms24043754.
Alzheimer's disease (AD) is the most common neurodegenerative disease in the world. It is classified as familial and sporadic. The dominant familial or autosomal presentation represents 1-5% of the total number of cases. It is categorized as early onset (EOAD; <65 years of age) and presents genetic mutations in (), (), or the (). Sporadic AD represents 95% of the cases and is categorized as late-onset (LOAD), occurring in patients older than 65 years of age. Several risk factors have been identified in sporadic AD; aging is the main one. Nonetheless, multiple genes have been associated with the different neuropathological events involved in LOAD, such as the pathological processing of Amyloid beta (Aβ) peptide and Tau protein, as well as synaptic and mitochondrial dysfunctions, neurovascular alterations, oxidative stress, and neuroinflammation, among others. Interestingly, using genome-wide association study (GWAS) technology, many polymorphisms associated with LOAD have been identified. This review aims to analyze the new genetic findings that are closely related to the pathophysiology of AD. Likewise, it analyzes the multiple mutations identified to date through GWAS that are associated with a high or low risk of developing this neurodegeneration. Understanding genetic variability will allow for the identification of early biomarkers and opportune therapeutic targets for AD.
阿尔茨海默病（AD）是世界上最常见的神经退行性疾病。它分为家族性和散发性。显性家族性或常染色体表现代表总病例数的 1-5%。它分为早发性（EOAD；<65 岁）和在 ()、() 或 () 中出现遗传突变。散发性 AD 占病例的 95%，分为迟发性（LOAD），发生在 65 岁以上的患者中。在散发性 AD 中已经确定了几个风险因素；年龄是主要因素。然而，多个基因与 LOAD 中涉及的不同神经病理事件有关，例如淀粉样β (Aβ) 肽和 Tau 蛋白的病理性处理，以及突触和线粒体功能障碍、神经血管改变、氧化应激和神经炎症等。有趣的是，使用全基因组关联研究（GWAS）技术，已经确定了许多与 LOAD 相关的多态性。这篇综述旨在分析与 AD 病理生理学密切相关的新遗传发现。同样，它分析了迄今为止通过 GWAS 确定的与这种神经退行性变发生的高或低风险相关的多种突变。了解遗传变异性将有助于确定 AD 的早期生物标志物和适当的治疗靶点。
