Treatment by low-dose brain radiation therapy improves memory performances without changes of the amyloid load in the TgF344-AD rat model

•Low-dose radiation therapy (LD-RT) improves memory in 15-month-old TgF344-AD rats.•The effect of LD-RT on memory was not observed when 2 Gy x 5 were delivered weekly.•LD-RT did not induce amyloid or neuroinflammation changes in animals at this stage.•The advanced pathology at this stage might explain the lack of modulation by LD-RT. Alzheimer's disease (AD) is a neurodegenerative condition affecting memory performance. This pathology is characterized by intracerebral amyloid plaques and tau tangles coupled with neuroinflammation. During the last century, numerous therapeutic trials unfortunately failed highlighting the need to find new therapeutic approaches. Low-dose brain radiotherapy (LD-RT) showed efficacy to reduce amyloid load and inflammation in patients with peripheral diseases. In this study, the therapeutic potential of 2 LD-RT schedules was tested on the TgF344-AD rat model of AD. Fifteen-month-old rats were irradiated with 5 fractions of 2 Gy delivered either daily or weekly. The daily treatment induced an improvement of memory performance in the Y-maze. In contrast, the weekly treatment increased the microglial reactivity in the hippocampus. A lack of effect of both regimens on amyloid pathology was unexpectedly observed. The positive effect on cognition encourages to further evaluate the LD-RT therapeutic potential and highlights the impact of the design choice of the LD-RT regimen.