Photobiomodulation in experimental models of Alzheimer's disease: state-of-the-art and translational perspectives

Abstract

Alzheimer's disease (AD) poses a significant public health problem, affecting millions of people across the world. Despite decades of research into therapeutic strategies for AD, effective prevention or treatment for this devastating disorder remains elusive. In this review, we discuss the potential of photobiomodulation (PBM) for preventing and alleviating AD-associated pathologies, with a focus on the biological mechanisms underlying this therapy. Future research directions and guidance for clinical practice for this non-invasive and non-pharmacological therapy are also highlighted. The available evidence indicates that different treatment paradigms, including transcranial and systemic PBM, along with the recently proposed remote PBM, all could be promising for AD. PBM exerts diverse biological effects, such as enhancing mitochondrial function, mitigating the neuroinflammation caused by activated glial cells, increasing cerebral perfusion, improving glymphatic drainage, regulating the gut microbiome, boosting myokine production, and modulating the immune system. We suggest that PBM may serve as a powerful therapeutic intervention for AD.

Keywords: Alzheimer’s disease (AD); Experimental models; Neurodegeneration; Photobiomodulation (PBM); Therapy.

Fig. 1

Overview of different PBM treatment paradigms for AD and an illustration showing the mechanisms traditionally considered to underlie the action of PBM. Abbreviations: LED, light-emitting diode; PBM, photobiomodulation; CCO, cytochrome c oxidase; ATP, adenosine triphosphate; NO, nitric oxide

Fig. 2

Summary of signaling pathways activated by transcranial PBM and subsequent biological effects. Abbreviations: PBM, photobiomodulation; RTKs, receptor tyrosine kinases; AMPAR, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor; IDE, insulin-degrading enzyme; CREB, cAMP response element-binding protein; BNDF, brain-derived neurotrophic factor; CCO, cytochrome c oxidase; APP; amyloid precursor protein; PGC1-α, peroxisome proliferator-activated receptor gamma coactivator 1-alpha; PPARγ, peroxisome proliferator-activated receptor gamma; ADAM10, a disintegrin and metalloproteinase domain-containing protein 10; TGFβ-1, transforming growth factor beta 1, TGFβR, transforming growth factor beta receptor; BMP, bone morphogenetic protein; BMPR; Bone morphogenetic protein receptor; ROS, reactive oxygen species

Fig. 3

Additional proposed mechanisms of action for transcranial PBM. Abbreviations: PBM, photobiomodulation; ROS, reactive oxygen species; Aβ, amyloid beta; NO, nitrogen oxide; CSF, cerebrospinal fluid; AQP4, aquaporin 4; ISF, interstitial fluid

Fig. 4

Proposed mechanisms of action for systemic and remote PBM. Abbreviations: PBM, photobiomodulation; ROS, reactive oxygen species; IFNγ, interferon gamma; IL-10, interleukin 10; TGFβ-1, transforming growth factor beta 1; IGF-1, insulin-like growth factor 1; BNDF, brain-derived neurotrophic factor; Aβ, amyloid beta; PGC1-α, peroxisome proliferator-activated receptor gamma coactivator 1-alpha; FNDC5, fibronectin type III domain-containing protein 5

Fig. 5

Summary of directions for future research and the clinical translation of PBM therapy. Abbreviations: PBM, photobiomodulation; AD, Alzheimer’s disease; CSF, cerebrospinal fluid