Modulation of glymphatic system by visual circuit activation alleviates memory impairment and apathy in a mouse model of Alzheimer’s disease

Wen Wu (), Yubai Zhao, Xin Cheng, Xiaoru Xie, Yixiu Zeng, Quan Tao, Yishuai Yang, Chuan Xiao, Zhan Zhang, Jiahui Pang, Jian Jin, Hongbo He, Yangyang Lin, Boxing Li, Junxian Ma (), Xiaojing Ye () and Wei-Jye Lin ()
Additional contact information
Wen Wu: Zhujiang Hospital, Southern Medical University
Yubai Zhao: Zhujiang Hospital, Southern Medical University
Xin Cheng: Sun Yat-sen University
Xiaoru Xie: Sun Yat-sen University
Yixiu Zeng: Sun Yat-sen University
Quan Tao: Zhujiang Hospital, Southern Medical University
Yishuai Yang: Sun Yat-sen University
Chuan Xiao: Sun Yat-sen University
Zhan Zhang: Sun Yat-sen University
Jiahui Pang: Zhujiang Hospital, Southern Medical University
Jian Jin: Zhujiang Hospital, Southern Medical University
Hongbo He: Southern Medical University
Yangyang Lin: the Sixth Affiliated Hospital, Sun Yat-sen University
Boxing Li: Sun Yat-sen University
Junxian Ma: Tianfu Xinglong Lake Laboratory
Xiaojing Ye: Sun Yat-sen University
Wei-Jye Lin: Sun Yat-sen University

Nature Communications, 2025, vol. 16, issue 1, 1-20

Abstract: Abstract Alzheimer’s disease is characterized by progressive amyloid deposition and cognitive decline, yet the pathological mechanisms and treatments remain elusive. Here we report the therapeutic potential of low-intensity 40 hertz blue light exposure in a 5xFAD mouse model of Alzheimer’s disease. Our findings reveal that light treatment prevents memory decline in 4-month-old 5xFAD mice and motivation loss in 14-month-old 5xFAD mice, accompanied by restoration of glial water channel aquaporin-4 polarity, improved brain drainage efficiency, and a reduction in hippocampal lipid accumulation. We further demonstrate the beneficial effects of 40 hertz blue light are mediated through the activation of the vLGN/IGL-Re visual circuit. Notably, concomitant use of anti-Aβ antibody with 40 hertz blue light demonstrates improved soluble Aβ clearance and cognitive performance in 5xFAD mice. These findings offer functional evidence on the therapeutic effects of 40 hertz blue light in Aβ-related pathologies and suggest its potential as a supplementary strategy to augment the efficacy of antibody-based therapy.

Date: 2025
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DOI: 10.1038/s41467-024-55678-w

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