Abstract
AB018. Monte Carlo simulations and in-vitro experiment to study if β-amyloid aggregates in Alzheimer’s disease can be damaged by low energy neutron capture
Saverio Altieri1,2, Diego Alberti3, Valeria Bitonto3, Sebastiano Maria Salomone Micocci3, Simonetta Geninatti-Crich3, Annamaria Deagostino4, Emanuele Azzi4, Polyssena Renzi4, Nicoletta Protti1,2, Valeria Pascali1,2
1Physics Department, University of Pavia, Pavia, Italy;
2National Institute for Nuclear Physics (INFN), University of Pavia, Pavia, Italy;
3Department of Biotechnology and Health Sciences, University of Torino, Torino, Italy;
4Department of Chemistry, University of Torino, Torino, Italy
Correspondence to: Valeria Pascali, MD. Physics Department, University of Pavia, Pavia, Italy; National Institute for Nuclear Physics (INFN), University of Pavia, via Agostino Bassi, 6, Pavia 27100, Italy. Email: valeria.pascali01@universitadipavia.it.
Background: Alzheimer’s disease (AD) is a neurodegenerative disorder that impairs nervous cells functions. One of AD’s main aspects is the overproduction of the β-amyloid (Aβ) protein which accumulates in the brain. Aggregates vary in size and shape from oligomers (spheres with a radius of few nm) which bind to form fibrils (tens of μm in length) up to plaques (spheres with a diameter of few μm). NECTAR (NEutron Capture enhanced Treatment of neurotoxic Amyloid aggRegates) project, funded by the European Commission, aims to study the effectiveness of low-energy capture-enhanced neutron irradiation (CENI) in the degradation of Aβ aggregates. CENI’s efficacy should be possible thanks to the combined action of high-LET particles and gamma produced by neutron capture reactions: the ranges of the former couple well with the Aβ aggregates size, causing them to be completely damaged; gamma, instead, acts over long distances by activating glia cells promoting further clearance.
Methods: The first steps of the experimental activity involve in-vitro irradiations of Aβ samples enriched with specifically designed borate compounds. These were irradiated inside the thermal column of the Triga Mark II nuclear research reactor, varying power and irradiation times. The in-vitro work was accompanied by preliminary Monte Carlo simulations (using the PHITS code) at macro- and microscopic scales conducted in order to obtain a first energy distributions within protein aggregates of different sizes.
Results: Although these were the very first in-vitro irradiations in the NECTAR project scenario, significant depolymerization of Aβ fibrils was observed in the irradiated samples. It is worth noting that the irradiations were conducted at the maximum power of the nuclear reactor (250 kW) and with very long times (about 1 h). It is, therefore, important to find the optimal conditions that may allow to reduce the irradiation time in relation to a future treatment extension AD patients.
Conclusions: From these very preliminary activities, encouraging results were observed. This prompts us to move forward by conducting more in-depth studies to demonstrate the validity of neutron capture therapy (NCT) principles applied in the treatment of a neurodegenerative disease such as AD.
Keywords: Neutron capture therapy (NCT); Alzheimer’s disease (AD); microdosimetry; nanoparticles
Acknowledgments
The authors acknowledge the colleagues of the Applied Nuclear Energy Laboratory (LENA) of the University of Pavia, where the Triga Mark II research nuclear reactor is housed, for their availability during the irradiation activity.
Funding: None.
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tro.amegroups.com/article/view/10.21037/tro-25-ab018/coif). The authors have no conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study involved only in-vitro experiments using irradiated samples and was conducted following established laboratory protocols and safety guidelines.
Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the noncommercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
doi: 10.21037/tro-25-ab018
Cite this abstract as: Altieri S, Alberti D, Bitonto V, Micocci SMS, Geninatti-Crich S, Deagostino A, Azzi E, Renzi P, Protti N, Pascali V. AB018. Monte Carlo simulations and in-vitro experiment to study if β-amyloid aggregates in Alzheimer’s disease can be damaged by low energy neutron capture. Ther Radiol Oncol 2025;9:AB018.
