Zhou Ting, Zhang Renlong, Ohulchanskyy Tymish Y, Qu Junle
School of Medical and Health Engineering, Changzhou University, Changzhou, China.
Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Physics and Optoelectronic Engineering, Shenzhen University, Shenzhen 518060, China.
Biomed Opt Express. 2025 Feb 24;16(3):1143-1155. doi: 10.1364/BOE.549594. eCollection 2025 Mar 1.
The accumulation of beta-amyloid (Aβ) peptide aggregates, commonly known as plaques, is considered a key hallmark in the development of Alzheimer's disease (AD). Recently, low-level light therapy (LLLT), also referred to as photobiomodulation (PBM), has emerged as a promising treatment approach for AD. Previous studies have shown that PBM reduces Aβ load primarily by enhancing the clearance capabilities of glia cells. However, it remains unclear whether PBM can directly reduce the formation of Aβ plaques in neuronal cells independent of the glia cell effect. In this study, we employed three-dimensional (3D) cultured HEK 293 APPsw cells as an AD model to investigate the impact of PBM on Aβ aggregation. We demonstrated that label-free two-photon excited fluorescence (TPEF) imaging and second harmonic generation (SHG) imaging are effective tools for monitoring Aβ aggregation in 3D cell models. The TPEF imaging results and subsequent quantification revealed that PBM, particularly with low-level near-infrared light from an 808 nm laser (compared to 1064, 1210, and 1470 nm lasers), significantly reduced Aβ aggregation, specifically plaques formation, in the 3D cultured cells, with the effect found to be dose-dependent. Moreover, a comprehensive analysis of protein expression in the 3D cultured cells revealed that PBM induces overexpression of the LRP1 receptor, which mediates Aβ degradation and thus leads to the reduction of Aβ aggregation. This study highlights the use of label-free nonlinear optical imaging to monitor Aβ aggregation in AD progression and provides novel insights into the effects of PBM on Aβ plaque formation in AD models.
β-淀粉样蛋白（Aβ）肽聚集体的积累，通常称为斑块，被认为是阿尔茨海默病（AD）发展的关键标志。最近，低强度光疗法（LLLT），也称为光生物调节（PBM），已成为一种有前途的AD治疗方法。先前的研究表明，PBM主要通过增强神经胶质细胞的清除能力来降低Aβ负荷。然而，尚不清楚PBM是否能独立于神经胶质细胞效应直接减少神经元细胞中Aβ斑块的形成。在本研究中，我们使用三维（3D）培养的HEK 293 APPsw细胞作为AD模型，研究PBM对Aβ聚集的影响。我们证明，无标记双光子激发荧光（TPEF）成像和二次谐波产生（SHG）成像是监测3D细胞模型中Aβ聚集的有效工具。TPEF成像结果及随后的定量分析表明，PBM，特别是来自808 nm激光的低强度近红外光（与1064、1210和1470 nm激光相比），显著减少了3D培养细胞中的Aβ聚集，特别是斑块形成，且发现该效应具有剂量依赖性。此外，对3D培养细胞中蛋白质表达的综合分析表明，PBM诱导LRP1受体的过表达，该受体介导Aβ降解，从而导致Aβ聚集的减少。本研究强调了使用无标记非线性光学成像来监测AD进展过程中的Aβ聚集，并为PBM对AD模型中Aβ斑块形成的影响提供了新的见解。
