Journal of Neuroinflammation (Dec 2022)

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

  • Kelly Ceyzériat,
  • Thomas Zilli,
  • Philippe Millet,
  • Nikolaos Koutsouvelis,
  • Giovanna Dipasquale,
  • Christine Fossey,
  • Thomas Cailly,
  • Frédéric Fabis,
  • Giovanni B. Frisoni,
  • Valentina Garibotto,
  • Benjamin B. Tournier

DOI
https://doi.org/10.1186/s12974-022-02673-x
Journal volume & issue
Vol. 19, no. 1
pp. 1 – 13

Abstract

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Abstract Preclinical studies have recently evaluated the impact of low-dose brain radiation therapy (LD-RT) in animal models of Alzheimer’s disease (AD) showing anti-amyloid and anti-inflammatory effects of this treatment. Its effectiveness varied, however, depending on the LD-RT protocol used and the stage when the treatment was applied. In this study, we aimed to evaluate the therapeutic potential of 10 Gy delivered in five daily fractions of 2 Gy (a protocol previously shown to induce an improvement of cognitive performances) in 9-month-old TgF344-AD rats, modeling at a pre-symptomatic stage of the disease. We showed that at an early stage, LD-RT was able to lower levels of the 18-kDa translocator protein (TSPO)-mediated neuroinflammation to normal ranges in addition to the secreted CLUSTERIN, another inflammatory protein also involved in Aβ aggregation. In addition, we demonstrated that LD-RT reduces all amyloid forms (~ − 60 to − 80%, P < 0.01; soluble and aggregated forms of Aβ40, Aβ42, and Aβoligomers). Interestingly, we showed for the first time that sAPPα levels were improved by the treatment, showing a higher activation of the non-amyloidogenic pathway, that could favor neuronal survival. The current evidence confirms the capacity of LD-RT to successfully modulate two pathological hallmarks of AD, namely amyloid and neuroinflammation, when applied before symptoms onset.

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