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

Published inJournal of neuroinflammation, vol. 19, no. 1, 311
Publication date2022-12-22
First online date2022-12-22
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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Keywords
  • Alzheimer’s disease
  • Amyloid
  • Low-dose
  • Neuroinflammation
  • Radiotherapy
  • Rats
  • Animals
  • Amyloid beta-Peptides / metabolism
  • Clusterin / metabolism
  • Clusterin / pharmacology
  • Neuroinflammatory Diseases
  • Alzheimer Disease / metabolism
  • Brain / metabolism
  • Amyloid / metabolism
  • Disease Models, Animal
  • Carrier Proteins / metabolism
  • Receptors, GABA-A
Citation (ISO format)
CEYZERIAT, Kelly et al. Low-dose brain irradiation normalizes TSPO and CLUSTERIN levels and promotes the non-amyloidogenic pathway in pre-symptomatic TgF344-AD rats. In: Journal of neuroinflammation, 2022, vol. 19, n° 1, p. 311. doi: 10.1186/s12974-022-02673-x
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ISSN of the journal1742-2094
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