Rajič Bumber Jelena, Rački Valentino, Mežnarić Silvestar, Pelčić Gordana, Mršić-Pelčić Jasenka
Department of Basic and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia.
Department of Neurology, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia.
J Clin Med. 2025 Aug 26;14(17):6047. doi: 10.3390/jcm14176047.
Apolipoprotein E (APOE) remains the most robust and widely replicated genetic risk factor for late-onset Alzheimer's disease (AD) susceptibility, with the ε4 allele () demonstrating profound associations with accelerated symptom manifestation, enhanced disease trajectory, and modified therapeutic responsiveness. This comprehensive review synthesizes contemporary evidence regarding the clinical utility of genotyping, emphasizing its integration into personalized therapeutic frameworks and early diagnostic paradigms. The APOE4 variant exerts pathogenic influence through impaired amyloid-β clearance, enhanced tau pathology, and compromised neuronal repair mechanisms that alter disease phenotype. We systematically examine available genotyping methodologies, encompassing polymerase chain reaction (PCR) and next-generation sequencing (NGS) platforms, and evaluate their practical implementation within clinical environments. Recent investigations demonstrate that status profoundly influences therapeutic efficacy, particularly with anti-amyloid interventions such as lecanemab, where carriers exhibit enhanced treatment response alongside increased adverse event susceptibility. Emerging gene therapeutic approaches show promise in mitigating -associated risks through targeted molecular interventions. The integration of genotyping with fluid biomarkers and neuroimaging techniques enables refined patient stratification and enhanced diagnostic precision, facilitating earlier intervention windows that optimize therapeutic outcomes before irreversible neuronal damage occurs. This review underscores testing as a transformative component of precision medicine in AD management, emphasizing its contribution to diagnostic refinement, clinical decision support, and targeted therapeutic interventions.
载脂蛋白E（APOE）仍然是晚发性阿尔茨海默病（AD）易感性最强且得到广泛重复验证的遗传风险因素，ε4等位基因与症状加速显现、疾病进展加快以及治疗反应改变密切相关。这篇综述综合了有关基因分型临床应用的当代证据，强调将其纳入个性化治疗框架和早期诊断模式。APOE4变体通过损害淀粉样蛋白β清除、增强tau病理以及损害神经元修复机制来影响疾病表型。我们系统地研究了现有的基因分型方法，包括聚合酶链反应（PCR）和下一代测序（NGS）平台，并评估了它们在临床环境中的实际应用。最近的研究表明，APOE状态对治疗效果有深远影响，特别是在使用如lecanemab等抗淀粉样蛋白干预措施时，携带者在治疗反应增强的同时不良事件易感性也增加。新兴的基因治疗方法有望通过靶向分子干预降低与APOE相关的风险。将APOE基因分型与液体生物标志物和神经成像技术相结合，能够实现更精确的患者分层并提高诊断精度，在不可逆的神经元损伤发生之前，促成更早的干预时机，从而优化治疗效果。这篇综述强调了APOE检测作为AD管理中精准医学的变革性组成部分，突出了其对诊断细化、临床决策支持和靶向治疗干预的贡献。
