Photobiomodulation, by utilizing low-power light in the visible and near-infrared spectra to trigger biological responses in cells and tissues, has been considered as a possible therapeutic strategy for Alzheimer’s disease (AD), while its specific mechanisms have remained elusive. Here, we demonstrate that cognitive and memory impairment in an AD mouse model can be ameliorated by 1070-nm light via reducing cerebral β-amyloid (Aβ) burden, the hallmark of AD. The glial cells, including microglia and astrocytes, play important roles in Aβ clearance. Our results show that 1070-nm light pulsed at 10 Hz triggers microglia rather than astrocyte responses in AD mice. The 1070-nm light-induced microglia responses with alteration in morphology and increased colocalization with Aβ are sufficient to reduce Aβ load in AD mice. Moreover, 1070-nm light pulsed at 10 Hz can reduce perivascular microglia and promote angiogenesis to further enhance Aβ clearance. Our study confirms the important roles of microglia and cerebral vessels in the use of 1070-nm light for the treatment of AD mice and provides a framework for developing a novel therapeutic approach for AD.

Near‐infrared photobiomodulation has been identified as a potential strategy for Alzheimer's disease (AD). However, the mechanisms underlying this therapeutic effect remain poorly characterize. Herein, it is illustrate that 1070‐nm light induces the morphological alteration of microglia from an M1 to M2 phenotype that secretes exosomes, which alleviates the β‐amyloid burden to improve cognitive function by ameliorating neuroinflammation and promoting neuronal dendritic spine plasticity. The results show that 4 J cm⁻² 1070‐nm light at a 10‐Hz frequency prompts microglia with an M1 inflammatory type to switch to an M2 anti‐inflammatory type. This induces secretion of M2 microglial‐derived exosomes containing miR‐7670‐3p, which targets activating transcription factor 6 (ATF6) during endoplasmic reticulum (ER) stress. Moreover, it is found that miR‐7670‐3p reduces ATF6 expression to further ameliorate ER stress, thus attenuating the inflammatory response and protecting dendritic spine integrity of neurons in the cortex and hippocampus of 5xFAD mice, ultimately leading to improvements in cognitive function. This study highlights the critical role of exosomes derive from 1070‐nm light‐modulated microglia in treating AD mice, which may provide a theoretical basis for the treatment of AD with the use of near‐infrared photobiomodulation.

Blood-brain barrier (BBB) disruption is frequently observed in the glioma region. However, the tumor uptake of drugs is still too low to meet the threshold of therapeutic purpose.