Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia.
Department of Radiology and Medical Imaging, Faculty of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Alkharj, Saudi Arabia.
J Alzheimers Dis. 2024;101(s1):S467-S477. doi: 10.3233/JAD-231277.
Alzheimer's disease (AD) is a progressive neurocognitive disorder. There is no cure for AD. Maintenance on intracellular levels of nicotinamide adenine dinucleotide (NAD+) has been reported to be a promising therapeutic strategy for the treatment of AD. NAD+ precursors that represent candidate targets include nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR).
This systematic review provides insights into the potential therapeutic value of NAD+ precursors including NMN and NR, for the treatment of AD using preclinical and clinical studies published in the last 5 years.
The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) protocol was followed to systematically search the literature using two databases.
We found 3 studies that used NMN to treat AD in preclinical murine models. However, human clinical trials using NMN as a therapeutic intervention in AD was not available in the current literature. We also found 4 studies that investigated the potential benefits of NR for the treatment of AD in preclinical models. We also found 2 human clinical trials that showed marked improvements in plasma and neuroimaging biomarkers, and cognitive measures following supplementation with NR.
Results of preclinical and clinical studies confirm the potential benefits of NAD+ precursors for the treatment of AD. However, further clinical studies are required to confirm the increasingly important value of NAD+ precursors as effective pharmacological interventions in the clinic.
阿尔茨海默病(AD)是一种进行性神经认知障碍。目前尚无治愈 AD 的方法。有报道称,维持细胞内烟酰胺腺嘌呤二核苷酸(NAD+)水平是治疗 AD 的一种有前途的治疗策略。NAD+前体作为候选靶点,包括烟酰胺单核苷酸(NMN)和烟酰胺核苷(NR)。
本系统评价综述了近 5 年来使用临床前和临床研究评估 NAD+前体(包括 NMN 和 NR)治疗 AD 的潜在治疗价值。
本研究按照系统评价和荟萃分析的首选报告项目(PRISMA)方案,使用两个数据库系统地检索文献。
我们发现了 3 项使用 NMN 治疗 AD 临床前小鼠模型的研究。然而,目前的文献中没有关于 NMN 作为 AD 治疗干预的人体临床试验。我们还发现了 4 项研究,调查了 NR 治疗 AD 临床前模型的潜在益处。我们还发现了 2 项人体临床试验,表明在补充 NR 后,血浆和神经影像学生物标志物以及认知测量有显著改善。
临床前和临床研究的结果证实了 NAD+前体治疗 AD 的潜在益处。然而,需要进一步的临床研究来确认 NAD+前体作为有效的药理学干预手段在临床上日益重要的价值。