Amelioration of Alzheimer's Disease Pathology in Zebrafish by Photobiomodulation

Background/Objectives: The zebrafish is a widely used research model due to its characteristics, such as being transparent during development, sharing 70% of its genes with humans, and having conserved features of vertebrate aging, including deterioration of mitochondrial and cognitive functions. While affecting approximately 15% of the world population, neurodegenerative diseases, such as Alzheimer's disease (AD), are currently incurable, requiring testing of alternative treatment strategies. Hence, this study was conducted to test the hypothesis that an optimized photobiomodulation (PBM) therapy improves AD pathology through its multifaceted beneficial effects, including enhancing mitochondrial function and reducing oxidative stress and neuroinflammation. Methods: A pharmacological zebrafish model of AD was developed by adding small amounts (100 nM) of okadaic acid (OKA) directly to fish tanks for nine days. Next, some of OKA-treated and control zebrafish were subjected to an optimized near-infrared PBM therapy while others remain untreated. Results: When examined after OKA treatment, zebrafish brains displayed histological hallmarks of AD including, neurofibrillary tangles, vacuoles, and neuroinflammation. Behavioral tests using a T-maze revealed that OKA-treated zebrafish spent significantly less time in the reward arm than untreated controls (15.2% vs. 50%). In contrast, a sequential PBM therapy significantly reduced formation of neurofibrillary tangles, vacuoles, neuroinflammation, and improved mitochondrial biogenesis in brains of OKA-treated zebrafish while also improving their cognitive function as evidenced by being able to recall the reward arm and spending more time there similar to controls (55 and 57%, respectively). Conclusions: These findings suggest that (1) a fast, cost-effective zebrafish AD model can be developed using OKA treatment and (2) PBM therapy holds promise to ameliorate AD pathology.