Affiliations: [a] Protontherapy Unit, Hospital of Trento, Azienda Provinciale per i Servizi Sanitari (APSS), Trento, Italy
| [b] Department of Neurosciences, Biomedicine & Movement Sciences, University of Verona, Verona, Italy | [c]
Verona University Hospital, Verona, Italy
Correspondence:
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Correspondence to: Stefano Tamburin, MD, PhD, Section of Neurology, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Piazzale Scuro 10, I-37134 Verona, Italy. Tel.: +39 347 523 5580; Fax: +39 045 802 7276; E-mail: stefano.tamburin@univr.it.; ORCID: 0000-0002-1561-2187.
Abstract: Amyloid-β deposition is one of the neuropathological hallmarks of Alzheimer’s disease (AD), but pharmacological strategies toward its reduction are poorly effective. Preclinical studies indicate that low-dose radiation therapy (LD-RT) may reduce brain amyloid-β. Animal models and proof-of-concept preliminary data in humans have shown that magnetic resonance guided focused ultrasound (MRgFUS) can reversibly open the blood-brain-barrier and facilitate the delivery of targeted therapeutics to the hippocampus, to reduce amyloid-β and promote neurogenesis in AD. Ongoing clinical trials on AD are exploring whole-brain LD-RT, which may damage radio-sensitive structures, i.e., hippocampus and white matter, thus contributing to reduced neurogenesis and radiation-induced cognitive decline. However, selective irradiation of cortical amyloid-β plaques through advanced LD-RT techniques might spare the hippocampus and white matter. We propose combined use of advanced LD-RT and targeted drug delivery through MRgFUS for future clinical trials to reduce amyloid-β deposition in AD since its preclinical stages.
Keywords: Alzheimer’s disease, amyloid-β
, blood-brain barrier, clinical trial, drug delivery, health technology, hippocampus, magnetic resonance guided focused ultrasound, radiation therapy, therapy
