Photobiomodulation attenuates Alzheimer’s-associated pathology and improves cognition

Abstract

Alzheimer’s disease (AD) is the most common form of dementia in elderly people, causing neuronal degeneration and cognitive deficits that significantly impair independence and quality of life for those affected and their families. Though AD is a major neurodegenerative disease with large amounts of research funding, there is no effective treatment to cure AD or slow its progression. Photobiomodulation (PBM) has shown its neuroprotective effect on multiple brain diseases in both animal models and human studies. However, the effect of long-term PBM treatment with continuous-wave low-level laser on AD and its underlying mechanism remains unclear. Using a transgenic AD rat model, long-term PBM treatment of two minutes was initiated at two-months of age 3 times/week for 16 months. The typical pathologies of AD, including memory loss, amyloid plaques, tau hyperphosphorylation, neuronal degeneration, spine damage, and synaptic loss were significantly improved with PBM treatment. Our further molecular studies revealed that PBM treatment: 1) recruits microglia surrounding amyloid plaques and improves microglial Aβ clearance by enhancing the expression of astrocytic IL-3 and microglial IL-3Rα; 2) regulates microglial and astrocytic phenotype from a neurotoxic phenotype (Microglial M1 and astrocytic A1 phenotype) to a neurotrophic phenotype (Microglial M2 and astrocytic A2 phenotype) and inhibits neuroinflammation; 3) preserves mitochondrial dynamics and alleviates oxidative stress; and 4) preserves neuronal hemoglobin. Notably, neuronal hemoglobin knockdown abolished the neuroprotective effect of PBM treatment. Taken together, our study demonstrated that multi-factors contribute to the beneficial effect of PBM on AD, and the mitochondrial-neuronal hemoglobin pathway is the target of PBM and plays a central role in the regulation of other factors. Thus, our study supports the possible use of PBM treatment to prevent neurodegeneration in the early stages of AD and provides a novel mechanism of PBM treatment in neuroprotection.