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

Low-dose brain irradiation normalizes TSPO and CLUSTERIN levels and promotes the non-amyloidogenic pathway in pre-symptomatic TgF344-AD rats

“…A recent study showed this treatment (5 × 2 Gy daily) did not impact neuroinflammation marker (IBA1 and GFAP) levels in WT mice and did not alter cognitive performances of WT mice in the alternative Y maze test 1-, 2-, 3 or 4 weeks posttreatment [25], showing the safety of this regimen in WT animals. Moreover, we recently showed that this schedule was even able to improve memory deficits when applied at a stage with high amyloid load and neuroinflammation [24]. However, at this advanced amyloid stage, no measurable effects on amyloid plaques and inflammation were observed, possibly because of the severe pathology.…”

“…Considered one of the standard treatments of cancer, when delivered at low-to intermediate-doses, radiotherapy has been commonly used to treat a wide range of benign conditions, including amyloid deposits and chronic inflammation diseases [20]. In the brain, different fractionation protocols of LD-RT were tested in mouse and rat models of Alzheimer's disease at variable disease stages and post-treatment phases and the anti-amyloid and the anti-inflammatory effects of LD-RT were confirmed in most studies [21][22][23][24][25][26][27]. Indeed, we previously evaluated the therapeutic potential of LD-RT by comparing two different regimens (2 Gy × 5 fractions delivered weekly or daily) delivered at an advanced stage [24].…”

“…In the brain, different fractionation protocols of LD-RT were tested in mouse and rat models of Alzheimer's disease at variable disease stages and post-treatment phases and the anti-amyloid and the anti-inflammatory effects of LD-RT were confirmed in most studies [21][22][23][24][25][26][27]. Indeed, we previously evaluated the therapeutic potential of LD-RT by comparing two different regimens (2 Gy × 5 fractions delivered weekly or daily) delivered at an advanced stage [24]. We obtained promising therapeutic effects as the memory performances in the TgF344-AD rat model significantly improved when LD-RT was delivered in five consecutive days.…”

Control of Neuroinflammation through Radiation-Induced Microglial Changes

“…Arguably, the most important takeaway from this study is that, without radiation, Tg female mice have higher Aβ levels than Tg male mice; however, radiation reduced these levels in the female Tg mice, which correlated with decreased microglial activation as determined by CD68 receptor staining [176]. Recently, rat models of AD were also shown to have improved memory performance in response to a higher dose of ionising radiation of 2 Gy/day for 5 days, without increasing neuroinflammation or amyloid load [177]. LDIR has also been shown to promote an M2 morphology in LPS treated mice microglial (BV2) cells [25].…”

The Rationale for Radiation Therapy in Alzheimer's Disease

“…Studies in Geneva. The group from the University of Geneva in Switzerland were the first to respond to our novel studies ( 10 ) and published their initial results using the TgF344-AD model which presents the human APP Swedish and PS1 delta E9 transgenes in the Fisher rat 344 background in 2021 ( 11 ). In these experiments, 14-month-old female rats (at which age amyloid pathology and neuroinflammation are well-advanced) were treated with either 5 fractions of 2 Gy in 5 days or 5 fractions of 2 Gy once a week for 5 weeks.…”