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

Kelly Ceyzériat; Thomas Zilli; Aïda B Fall; Philippe Millet; Nikolaos Koutsouvelis; Giovanna Dipasquale; Giovanni B Frisoni; Benjamin B Tournier; Valentina Garibotto

doi:10.1016/j.neurobiolaging.2021.03.008

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

Neurobiol Aging. 2021 Jul:103:117-127. doi: 10.1016/j.neurobiolaging.2021.03.008. Epub 2021 Mar 23.

Authors

Kelly Ceyzériat¹, Thomas Zilli², Aïda B Fall³, Philippe Millet⁴, Nikolaos Koutsouvelis⁵, Giovanna Dipasquale⁵, Giovanni B Frisoni⁶, Benjamin B Tournier⁴, Valentina Garibotto⁷

Affiliations

¹ Division of Adult Psychiatry, Department of Psychiatry, Geneva University Hospitals, Geneva, Switzerland; Division of Nuclear Medicine and Molecular Imaging, Diagnostic Department, Geneva University Hospitals, and NimtLab, Faculty of Medicine, Geneva University, Geneva, Switzerland; Division of Radiation Oncology, Department of Oncology, Geneva University Hospitals, Geneva, Switzerland; Faculty of Medicine, Geneva University, Geneva, Switzerland.
² Division of Radiation Oncology, Department of Oncology, Geneva University Hospitals, Geneva, Switzerland; Faculty of Medicine, Geneva University, Geneva, Switzerland.
³ Division of Adult Psychiatry, Department of Psychiatry, Geneva University Hospitals, Geneva, Switzerland.
⁴ Division of Adult Psychiatry, Department of Psychiatry, Geneva University Hospitals, Geneva, Switzerland; Faculty of Medicine, Geneva University, Geneva, Switzerland.
⁵ Division of Radiation Oncology, Department of Oncology, Geneva University Hospitals, Geneva, Switzerland.
⁶ Memory Center, Geneva University Hospitals, and LANVIE, Faculty of Medicine, Geneva University, Geneva, Switzerland; IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
⁷ Division of Nuclear Medicine and Molecular Imaging, Diagnostic Department, Geneva University Hospitals, and NimtLab, Faculty of Medicine, Geneva University, Geneva, Switzerland. Electronic address: [email protected].

PMID: 33895629
DOI: 10.1016/j.neurobiolaging.2021.03.008

Abstract

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.

Keywords: Alzheimer's disease; Amyloid; Low-dose; Neuroinflammation; Radiotherapy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease / pathology
Alzheimer Disease / psychology*
Alzheimer Disease / radiotherapy*
Animals
Disease Models, Animal
Dose Fractionation, Radiation*
Female
Hippocampus / cytology
Memory*
Microglia / physiology
Neuroinflammatory Diseases
Rats
Rats, Inbred F344
Rats, Transgenic
Treatment Outcome