Svob Strac Dubravka, Konjevod Marcela, Sagud Marina, Nikolac Perkovic Matea, Nedic Erjavec Gordana, Vuic Barbara, Simic Goran, Vukic Vana, Mimica Ninoslav, Pivac Nela
Laboratory for Molecular Neuropsychiatry, Division of Molecular Medicine, Rudjer Boskovic Institute, Zagreb, Croatia.
Department of Psychiatry, Clinical Hospital Centre Zagreb, Zagreb, Croatia.
Pharmgenomics Pers Med. 2021 May 28;14:631-653. doi: 10.2147/PGPM.S284615. eCollection 2021.
Alzheimer's disease (AD) is a progressive, complex, and multifactorial neurodegenerative disorder, still without effective and stable therapeutic strategies. Currently, available medications for AD are based on symptomatic therapy, which include acetylcholinesterase (AChE) inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonist. Additionally, medications such as antipsychotic drugs, antidepressants, sedative, and hypnotic agents, and mood stabilizers are used for the management of behavioral and psychological symptoms of dementia (BPSD). Clinical research has been extensively investigated treatments focusing on the hallmark pathology of AD, including the amyloid deposition, tau hyperphosphorylation, neuroinflammation, and vascular changes; however, so far without success, as all new potential drugs failed to show significant clinical benefit. The underlying heterogeneous etiology and diverse symptoms of AD suggest that a precision medicine strategy is required, which would take into account the complex genetic, epigenetic, and environmental landscape of each AD patient. The article provides a comprehensive overview of the literature on AD, the current and potential therapy of both cognitive symptoms as well as BPSD, with a special focus on gut microbiota and epigenetic modifications as new emerging drug targets. Their specific patterns could represent the basis for novel individually tailored approaches aimed to optimize precision medicine strategies for AD prevention and treatment. However, the successful application of precision medicine to AD demands a further extensive research of underlying pathological processes, as well as clinical and biological complexity of this multifactorial neurodegenerative disorder.
阿尔茨海默病(AD)是一种进行性、复杂且多因素的神经退行性疾病,目前仍没有有效且稳定的治疗策略。目前,用于治疗AD的药物主要基于对症治疗,包括乙酰胆碱酯酶(AChE)抑制剂和N-甲基-D-天冬氨酸(NMDA)受体拮抗剂。此外,抗精神病药物、抗抑郁药、镇静催眠药和心境稳定剂等药物用于管理痴呆的行为和心理症状(BPSD)。临床研究广泛探索了针对AD标志性病理特征的治疗方法,包括淀粉样蛋白沉积、tau蛋白过度磷酸化、神经炎症和血管变化;然而,迄今为止均未成功,因为所有新的潜在药物均未显示出显著的临床益处。AD潜在的异质性病因和多样症状表明需要采用精准医学策略,该策略应考虑到每位AD患者复杂的遗传、表观遗传和环境因素。本文全面综述了关于AD的文献、认知症状以及BPSD的当前和潜在治疗方法,特别关注肠道微生物群和表观遗传修饰作为新兴的药物靶点。它们的特定模式可能代表了旨在优化AD预防和治疗精准医学策略的新型个体化方法的基础。然而,将精准医学成功应用于AD需要对潜在病理过程以及这种多因素神经退行性疾病的临床和生物学复杂性进行进一步广泛研究。