Indiana University School of Medicine, Indianapolis, IN, USA.
Department of Medicine, Division of General Internal Medicine and Geriatrics, Indiana University School of Medicine, Indianapolis, IN, USA.
Sci Rep. 2021 Jan 12;11(1):621. doi: 10.1038/s41598-020-77808-2.
Late Onset Alzheimer's Disease is the most common cause of dementia, characterized by extracellular deposition of plaques primarily of amyloid-β (Aβ) peptide and tangles primarily of hyperphosphorylated tau protein. We present data to suggest a noninvasive strategy to decrease potentially toxic Aβ levels, using repeated electromagnetic field stimulation (REMFS) in primary human brain (PHB) cultures. We examined effects of REMFS on Aβ levels (Aβ40 and Aβ42, that are 40 or 42 amino acid residues in length, respectively) in PHB cultures at different frequencies, powers, and specific absorption rates (SAR). PHB cultures at day in vitro 7 (DIV7) treated with 64 MHz, and 1 hour daily for 14 days (DIV 21) had significantly reduced levels of secreted Aβ40 (p = 001) and Aβ42 (p = 0.029) peptides, compared to untreated cultures. PHB cultures (DIV7) treated at 64 MHz, for 1 or 2 hour during 14 days also produced significantly lower Aβ levels. PHB cultures (DIV28) treated with 64 MHz 1 hour/day during 4 or 8 days produced a similar significant reduction in Aβ40 levels. 0.4 W/kg was the minimum SAR required to produce a biological effect. Exposure did not result in cellular toxicity nor significant changes in secreted Aβ precursor protein-α (sAPPα) levels, suggesting the decrease in Aβ did not likely result from redirection toward the α-secretase pathway. EMF frequency and power used in our work is utilized in human magnetic resonance imaging (MRI, thus suggesting REMFS can be further developed in clinical settings to modulate Aβ deposition.
迟发性阿尔茨海默病是痴呆症最常见的病因，其特征是细胞外淀粉样β（Aβ）肽主要沉积形成斑块和过度磷酸化tau 蛋白主要沉积形成缠结。我们提供的数据表明，使用重复电磁场刺激（REMFS）在原代人脑（PHB）培养物中是一种降低潜在毒性 Aβ水平的非侵入性策略。我们研究了不同频率、功率和比吸收率（SAR）的 REMFS 对 PHB 培养物中 Aβ水平（Aβ40 和 Aβ42，分别为 40 或 42 个氨基酸残基）的影响。在体外培养第 7 天（DIV7）的 PHB 培养物中，用 64MHz 治疗 1 小时，每天 1 次，共 14 天（DIV21），与未治疗的培养物相比，分泌的 Aβ40（p=0.001）和 Aβ42（p=0.029）肽水平显著降低。在第 14 天（DIV7）的 PHB 培养物中用 64MHz 治疗 1 或 2 小时也产生了显著更低水平的 Aβ。在第 28 天（DIV28）的 PHB 培养物中用 64MHz 治疗 1 小时/天，共 4 或 8 天，Aβ40 水平也显著降低。产生生物学效应所需的最小 SAR 为 0.4W/kg。暴露不会导致细胞毒性，也不会导致分泌的 Aβ前体蛋白-α（sAPPα）水平发生显著变化，这表明 Aβ 的减少可能不是由于转向 α-分泌酶途径。我们工作中使用的 EMF 频率和功率用于人类磁共振成像（MRI），因此表明 REMFS 可以在临床环境中进一步开发以调节 Aβ 沉积。
