Protontherapy Unit, Hospital of Trento, Azienda Provinciale per i Servizi Sanitari (APSS), Trento, Italy.
Department of Neurosciences, Biomedicine & Movement Sciences, University of Verona, Verona, Italy.
J Alzheimers Dis. 2021;84(1):69-72. doi: 10.3233/JAD-215041.
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.
淀粉样蛋白-β沉积是阿尔茨海默病（AD）的神经病理学标志之一，但针对其减少的药物治疗策略效果不佳。临床前研究表明，低剂量辐射疗法（LD-RT）可能减少大脑中的淀粉样蛋白-β。动物模型和人类的初步概念验证数据表明，磁共振引导聚焦超声（MRgFUS）可以可逆地打开血脑屏障，促进靶向治疗药物递送至海马体，以减少 AD 中的淀粉样蛋白-β并促进神经发生。正在进行的 AD 临床试验正在探索全脑 LD-RT，这可能会损害对辐射敏感的结构，即海马体和白质，从而导致神经发生减少和辐射诱导的认知能力下降。然而，通过先进的 LD-RT 技术选择性地辐照皮质淀粉样蛋白-β斑块可能会使海马体和白质免受影响。我们建议在未来的临床试验中联合使用先进的 LD-RT 和通过 MRgFUS 进行靶向药物输送，以从 AD 的临床前阶段开始减少淀粉样蛋白-β沉积。
