Maestría en Ciencias Farmacéuticas, Universidad Autónoma Metropolitana, Unidad Xochimilco, Coyoacán (México D.F.), Mexico; Departamento de Neurogenética, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Tlalpan (México D.F.), Mexico.
Departamento de Neurogenética, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Tlalpan (México D.F.), Mexico.
Neurologia (Engl Ed). 2022 May;37(4):287-303. doi: 10.1016/j.nrleng.2018.03.022. Epub 2020 Jun 1.
Alzheimer disease (AD) is the most common cause of dementia and is considered one of the main causes of disability and dependence affecting quality of life in elderly people and their families. Current pharmacological treatment includes acetylcholinesterase inhibitors (donepezil, galantamine, rivastigmine) and memantine; however, only one-third of patients respond to treatment. Genetic factors have been shown to play a role in this inter-individual variability in drug response.
We review pharmacogenetic reports of AD-modifying drugs, the pharmacogenetic biomarkers included, and the phenotypes evaluated. We also discuss relevant methodological considerations for the design of pharmacogenetic studies into AD. A total of 33 pharmacogenetic reports were found; the majority of these focused on the variability in response to and metabolism of donepezil. Most of the patients included were from Caucasian populations, although some studies also include Korean, Indian, and Brazilian patients. CYP2D6 and APOE are the most frequently studied biomarkers. The associations proposed are controversial.
Potential pharmacogenetic biomarkers for AD have been identified; however, it is still necessary to conduct further research into other populations and to identify new biomarkers. This information could assist in predicting patient response to these drugs and contribute to better treatment decision-making in a context as complex as ageing.
阿尔茨海默病（AD）是痴呆症最常见的病因，被认为是导致老年人及其家庭生活质量下降、残疾和依赖的主要原因之一。目前的药物治疗包括乙酰胆碱酯酶抑制剂（多奈哌齐、加兰他敏、利斯的明）和美金刚；然而，只有三分之一的患者对治疗有反应。遗传因素已被证明在药物反应的个体差异中起作用。
我们回顾了 AD 修饰药物的药物遗传学报告，包括的药物遗传学生物标志物以及评估的表型。我们还讨论了 AD 药物遗传学研究设计的相关方法学考虑因素。共发现 33 篇药物遗传学报告；其中大多数集中在多奈哌齐的反应和代谢的变异性上。大多数纳入的患者来自白种人群体，尽管一些研究还包括韩国、印度和巴西患者。CYP2D6 和 APOE 是最常研究的生物标志物。提出的关联存在争议。
已经确定了 AD 的潜在药物遗传学生物标志物；然而，仍有必要在其他人群中进行进一步的研究，并确定新的生物标志物。这些信息可以帮助预测患者对这些药物的反应，并有助于在老龄化等复杂背景下做出更好的治疗决策。
