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Combining Low-Dose Radiation Therapy and Magnetic Resonance Guided Focused Ultrasound to Reduce Amyloid-β Deposition in Alzheimer’s Disease
Journal of Alzheimer’s Disease ( IF 4 ) Pub Date : 2021-08-30 , DOI: 10.3233/jad-215041
Paolo Farace 1 , Stefano Tamburin 2, 3
Affiliation  

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.

中文翻译:

结合低剂量放射治疗和磁共振引导聚焦超声减少阿尔茨海默病中的β淀粉样蛋白沉积

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,但对其减少的药理学策略效果不佳。临床前研究表明,低剂量放射治疗 (LD-RT) 可能会减少脑淀粉样蛋白-β。动物模型和人类概念验证的初步数据表明,磁共振引导聚焦超声 (MRgFUS) 可以可逆地打开血脑屏障,促进靶向治疗药物向海马体的传递,减少淀粉样蛋白 β 并促进AD中的神经发生。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,即海马和白质,从而导致神经发生减少和辐射引起的认知能力下降。然而,通过先进的 LD-RT 技术选择性照射皮质淀粉样蛋白-β 斑块可能会保护海马体和白质。我们建议在未来的临床试验中结合使用先进的 LD-RT 和通过 MRgFUS 的靶向药物递送,以减少 AD 中自临床前阶段以来的淀粉样蛋白 β 沉积。
更新日期:2021-09-01
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