Affiliations: [a] Division of Adult Psychiatry, Department of Psychiatry, Geneva University Hospitals, Geneva, Switzerland
| [b] Division of Nuclear Medicine and Molecular Imaging, Diagnostic Department, Geneva University Hospitals, and NimtLab, Faculty of Medicine, Geneva University, Geneva, Switzerland
| [c] Division of Radiation Oncology, Department of Oncology, Geneva University Hospitals, Geneva, Switzerland
| [d] Faculty of Medicine, Geneva University, Geneva, Switzerland
| [e] Memory Center, Geneva University Hospitals, and LANVIE, Faculty of Medicine, Geneva University, Geneva, Switzerland
Correspondence:
[*]
Correspondence to: Thomas Zilli, Radiation Oncology, Geneva University Hospital, Avenue de la Roseraie, 53, 1205 Geneva, Switzerland. Tel.: +41 22 372 70 90; E-mail: Thomas.Zilli@hcuge.ch.
Abstract: Background: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. Objective: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. Methods: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. Results: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. Conclusion: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.
Keywords: Alzheimer’s disease, amyloid, neuroinflammation, radiation therapy, tau
