背景:阿尔茨海默病(AD)的病理生理标志包括细胞外淀粉样蛋白斑和细胞内神经原纤维缠结(NFT)。最近的研究也证明了神经炎症在疾病进展中的作用。使用低剂量放射治疗(LDRT)的临床试验和动物研究显示了AD的治疗潜力。这篇系统的综述总结了目前使用LDRT治疗AD的证据。概述了潜在的行动机制,并讨论了未来试验规划中的当前挑战.
方法:对人类和动物研究以及描述RT治疗AD结果的注册临床试验进行系统评价。我们遵循了2020年PRISMA指南。文章发表至7月1日,2023年,包括。
结果:最初的搜索产生了993篇文章。删除副本和不合格出版物后,总共16只(12只动物,4人)研究包括在内。在动物和人试验中使用各种剂量方案。结果表明,LDRT减少了淀粉样斑块和NFTs的数量,并在AD病理进程中参与的基因和蛋白表达调控中发挥作用。LDRT已证明星形胶质细胞增生和小胶质细胞增生减少,抗炎和神经保护作用以及减轻动物模型中认知缺陷的症状。大多数人类研究表明认知和行为的改善。没有一个试验或研究描述显著(>2级)毒性。
结论:临床前研究,动物研究,和早期的临床试验显示LDRT在治疗AD病理中的有希望的作用,尽管潜在的机制尚未得到充分探索。I/II/III期试验需要评估长期安全性,功效,以及LDRT在AD治疗中的最佳治疗参数。
OBJECTIVE: Pathophysiological hallmarks of Alzheimer\'s disease (AD) include extracellular amyloid plaques and intracellular neurofibrillary tangles. Recent studies also demonstrated a role of neuroinflammation in the progression of the disease. Clinical trials and animal studies using low-dose radiation therapy (LDRT) have shown therapeutic potential for AD. This systematic
review summarizes the current evidence on the use of LDRT for the treatment of AD, outlines potential mechanisms of action, and discusses current challenges in the planning of future trials.
METHODS: A systematic
review of human and animal studies as well as registered clinical trials describing outcomes for RT in the treatment of AD was conducted. We followed the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Articles published until July 1, 2023, were included.
RESULTS: The initial search yielded 993 articles. After the removal of duplicates and ineligible publications, a total of 16 (12 animal, 4 human) studies were included. Various dose regimens were utilized in both animal and human trials. The results revealed that LDRT reduced the number of amyloid plaques and neurofibrillary tangles, and it has a role in the regulation of genes and protein expression involved in the pathological progression of AD. LDRT has demonstrated reduced astro- and microgliosis, anti-inflammatory and neuroprotective effects, and an alleviation of symptoms of cognitive deficits in animal models. Most studies in humans suggested improvements in cognition and behavior. None of the trials or studies described significant (>grade 2) toxicity.
CONCLUSIONS: Preclinical studies, animal studies, and early clinical trials in humans have shown a promising role for LDRT in the treatment of AD pathologies, although the underlying mechanisms are yet to be fully explored. Phase I/II/III trials are needed to assess the long-term safety, efficacy, and optimal treatment parameters of LDRT in AD treatment.