Qin Wanqi, He Jiayi, Zhou Yi
School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China.
J Neurosci Methods. 2025 Jun;418:110428. doi: 10.1016/j.jneumeth.2025.110428. Epub 2025 Mar 17.
Transcranial focused ultrasound (TFU) is emerging as a promising non-invasive therapy capable of blood-brain barrier (BBB) opening. TFU potentially allows the transfer of therapeutic agents to targeted brain areas for patients affected with Alzheimer's disease (AD).
The efficacy and mechanism of TFU in modulating BBB permeability in key brain regions, including the hippocampus and frontal lobe, are investigated in this research. A total of 20 participants aged 60-85 years were involved with AD. The treatment protocol involved three TFU sessions, spaced three weeks apart. The research encompasses pre-assessment and post-assessment of treatment with follow-up ranging from 5 to 12 months.
Statistical analysis involved paired t-tests to compare pre- and post-treatment cognitive scores, and ANOVA to predict significant differences in amyloid reduction across different brain regions, with the high decrease observed in the hippocampus. Multivariate Analysis (MANOVA) to explore the combined effect of cognitive and amyloid data. Linear Regression Analysis to predict cognitive improvement from amyloid plaque reduction. Longitudinal analysis for time-to-event analysis assessing the durability of effects over time.
Florbetaben Positron Emission Tomography (PET) scans demonstrated a reduction in β-amyloid plaque burden, with a 15 % average decrease in the treated brain regions. No adverse effects on disease progression were observed up to 1 year after treatment.
This analysis presents the largest cohort of AD patients treated with TFU, with the longest follow-up to date. The treatment demonstrated safety and feasibility, with reversible BBB opening in multiple brain regions.
经颅聚焦超声（TFU）正成为一种有前景的非侵入性治疗方法，能够打开血脑屏障（BBB）。TFU有可能使治疗药物转移至患有阿尔茨海默病（AD）患者的靶向脑区。
本研究调查了TFU调节包括海马体和额叶在内的关键脑区血脑屏障通透性的疗效和机制。共有20名60 - 85岁的AD患者参与。治疗方案包括三次TFU治疗，间隔三周。该研究涵盖治疗前评估和治疗后评估，随访时间为5至12个月。
统计分析包括配对t检验以比较治疗前后的认知得分，以及方差分析以预测不同脑区淀粉样蛋白减少的显著差异，在海马体中观察到高度降低。采用多变量分析（MANOVA）探索认知和淀粉样蛋白数据的综合效应。采用线性回归分析从淀粉样斑块减少预测认知改善。进行纵向分析以进行事件时间分析，评估随时间变化的效应持续性。
氟贝他班正电子发射断层扫描（PET）显示β - 淀粉样斑块负担减轻，治疗脑区平均减少15%。治疗后长达1年未观察到对疾病进展的不良影响。
本分析展示了接受TFU治疗的最大队列AD患者，以及迄今为止最长的随访时间。该治疗显示出安全性和可行性，在多个脑区可实现可逆性血脑屏障开放。
