Luo_2024_Comput.Struct.Biotechnol.J_23_2230

Alzheimer's disease (AD) is an age-related neurodegenerative disorder. Transgenic and pharmacological AD models are extensively studied to understand AD mechanisms and drug discovery. However, they are time-consuming and relatively costly, which hinders the discovery of potential anti-AD therapeutics. Here, we established a new model of AD in larval zebrafish by co-treatment with aluminum chloride (AlCl(3)) and D-galactose (D-gal) for 72 h. In particular, exposure to 150 microM AlCl(3) + 40 mg/mL D-gal, 200 microM AlCl(3) + 30 mg/mL D-gal, or 200 microM AlCl(3) + 40 mg/mL D-gal successfully induced AD-like symptoms and aging features. Co-treatment with AlCl(3) and D-gal caused significant learning and memory deficits, as well as impaired response ability and locomotor capacity in the plus-maze and light/dark test. Moreover, increased acetylcholinesterase and beta-galactosidase activities, beta-amyloid 1-42 deposition, reduced telomerase activity, elevated interleukin 1 beta mRNA expression, and enhanced reactive oxygen species production were also observed. In conclusion, our zebrafish model is simple, rapid, effective and affordable, incorporating key features of AD and aging, thus may become a unique and powerful tool for high-throughput screening of anti-AD compounds in vivo.