Photostimulation of lymphatic clearance of β-amyloid from mouse brain: a new strategy for the therapy of Alzheimer's disease

Dongyu Li; Hao Lin; Silin Sun; Shaojun Liu; Zhang Liu; Yuening He; Jingtan Zhu; Jianyi Xu; Oxana Semyachkina-Glushkovskaya; Tingting Yu; Dan Zhu

doi:10.1007/s12200-023-00099-8

Photostimulation of lymphatic clearance of β-amyloid from mouse brain: a new strategy for the therapy of Alzheimer's disease

Front Optoelectron. 2023 Dec 14;16(1):45. doi: 10.1007/s12200-023-00099-8.

Authors

Dongyu Li^#^{1

2}, Hao Lin^#¹, Silin Sun¹, Shaojun Liu¹, Zhang Liu¹, Yuening He¹, Jingtan Zhu³, Jianyi Xu¹, Oxana Semyachkina-Glushkovskaya⁴, Tingting Yu⁵, Dan Zhu¹

Affiliations

¹ Britton Chance Center for Biomedical Photonics - MoE Key Laboratory for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics - Advanced Biomedical Imaging Facility, Huazhong University of Science and Technology, Wuhan, 430074, China.
² School of Optical Electronic Information, Huazhong University of Science and Technology, Wuhan, 430074, China.
³ Britton Chance Center for Biomedical Photonics - MoE Key Laboratory for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics - Advanced Biomedical Imaging Facility, Huazhong University of Science and Technology, Wuhan, 430074, China. zhujingtan@hust.edu.cn.
⁴ Department of Biology, Saratov State University, Saratov, 410012, Russia.
⁵ Britton Chance Center for Biomedical Photonics - MoE Key Laboratory for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics - Advanced Biomedical Imaging Facility, Huazhong University of Science and Technology, Wuhan, 430074, China. yutingting@hust.edu.cn.

^# Contributed equally.

Abstract

Alzheimer's disease (AD) is an age-related neurodegenerative disorder that poses a significant burden on socio-economic and healthcare systems worldwide. However, the currently available therapy of AD is limited, and new strategies are needed to enhance the clearance of β-amyloid (Aβ) protein and improve cognitive function. Photobiomodulation (PBM) is a non-invasive and effective therapeutic method that has shown promise in treating various brain diseases. Here, we demonstrate that 1267-nm PBM significantly alleviates cognitive decline in the 5xFAD mouse model of AD and is safe as it does not induce a significant increase in cortical temperature. Moreover, with the combination of 3D tissue optical clearing imaging and automatic brain region segmentation, we show that PBM-mediated reductions of Aβ plaques in different subregions of prefrontal cortex and the hippocampus are different. The PBM-induced lymphatic clearance of Aβ from the brain is associated with improvement of memory and cognitive functions in 5xFAD mice. Our results suggest that the modulation of meningeal lymphatic vessels (MLVs) should play an important role in promoting Aβ clearance. Collectively, this pilot study demonstrates that PBM can safely accelerate lymphatic clearance of Aβ from the brain of 5xFAD mice, promoting improvement of neurocognitive status of AD animals suggesting that PBM can be an effective and bedside therapy for AD.

Keywords: Alzheimer’s disease; Amyloid-β clearance; Meningeal lymphatic vessels; Photostimulation.