Division of Adult Psychiatry, Department of Psychiatry, Geneva University Hospitals, Geneva, Switzerland.
Division of Nuclear Medicine and Molecular Imaging, Diagnostic Department, Geneva University Hospitals, and NimtLab, Faculty of Medicine, Geneva University, Geneva, Switzerland.
J Alzheimers Dis. 2022;86(2):641-653. doi: 10.3233/JAD-215510.
Low-dose radiation therapy (LD-RT) has been shown to decrease amyloidosis or inflammation in systemic diseases and has recently been proposed as possible treatment of Alzheimer's disease (AD). A positive effect of LD-RT on tauopathy, the other marker of AD, has also been suggested. These effects have been shown in preclinical studies, but their mechanisms are still not well understood.
This study aimed to evaluate if anti-amyloid and anti-inflammatory effects of LD-RT can be observed at an early stage of the disease. Its impact on tauopathy and behavioral alterations was also investigated.
The whole brain of 12-month-old 3xTg-AD mice was irradiated with 10 Gy in 5 daily fractions of 2 Gy. Mice underwent behavioral tests before and 8 weeks post treatment. Amyloid load, tauopathy, and neuroinflammation were measured using histology and/or ELISA.
Compared with wild-type animals, 3xTg-AD mice showed a moderate amyloid and tau pathology restricted to the hippocampus, a glial reactivity restricted to the proximity of amyloid plaques. LD-RT significantly reduced Aβ42 aggregated forms (-71%) in the hippocampus and tended to reduce other forms in the hippocampus and frontal cortex but did not affect tauopathy or cognitive performance. A trend for neuroinflammation markers reduction was also observed.
When applied at an early stage, LD-RT reduced amyloid load and possibly neuroinflammation markers, with no impact on tauopathy. The long-term persistence of these beneficial effects of LD-RT should be evaluated in future studies.
低剂量辐射疗法（LD-RT）已被证明可减少系统性疾病中的淀粉样变性或炎症，并最近被提议作为阿尔茨海默病（AD）的可能治疗方法。LD-RT 对 AD 的另一个标志物 tau 病也有积极影响，这一观点也已被提出。这些影响已在临床前研究中得到证实，但它们的机制仍不清楚。
本研究旨在评估 LD-RT 是否可以在疾病的早期阶段观察到抗淀粉样蛋白和抗炎作用。还研究了其对 tau 病和行为改变的影响。
用 5 天每天 2Gy 的 5 次分割将 12 个月大的 3xTg-AD 小鼠的整个大脑照射 10Gy。在治疗前和 8 周后，小鼠接受行为测试。使用组织学和/或 ELISA 测量淀粉样蛋白负荷、tau 病和神经炎症。
与野生型动物相比，3xTg-AD 小鼠表现出局限于海马体的中等淀粉样蛋白和 tau 病理学，局限于淀粉样斑块附近的神经胶质反应。LD-RT 可显著降低海马体中的 Aβ42 聚集形式（-71%），并倾向于降低海马体和额叶皮质中的其他形式，但不影响 tau 病或认知表现。还观察到神经炎症标志物减少的趋势。
在早期应用时，LD-RT 可降低淀粉样蛋白负荷和可能的神经炎症标志物，对 tau 病无影响。未来的研究应评估 LD-RT 这些有益影响的长期持久性。
