Development of a Zebrafish Model for Rapid Drug Screening against Alzheimer’s Disease

Alzheimer's disease, the leading cause of dementia in the elderly, is a complex neurodegenerative disorder which leads to a progressive decline in cognitive functions.A rapid screening model is highly demanded for identification and evaluation of novel anti-Alzheimer's disease drugs from a large numbers of compounds.Until now, numerous studies utilized zebrafish model for drug discovery.Since aluminum can induce a similar biological activity in zebrafish as in Alzheimer patients, in this study, we developed a novel animal model using 3 to 5 day post-fertilization larval zebrafish by optimizing the doses and duration of aluminum chloride exposure.Six anti-Alzheimer's disease drugs with a variety of mechanisms were tested to validate the newly developed zebrafish model.Importantly, Rivastigmine, ThT, Flurbiprofen and AM-117 could increase the value of Dyskinesia Recovery Rate by 53.4-64%, 169.4-200%, 54.5-96% and 70.9-121%, respectively.Rivastigmine, Memantine, ThT, Flurbiprofen, Rosiglitazone and AM-117 improved the value of Response Efficiency by 86.6-175.1%,28.2-66.6%,127.2-236.5%,118.3-323.7%,26.6-140.8%and 70.2-161.4%,respectively.Our results suggest that the zebrafish model developed in this study could be a useful tool for high throughput screening of potential novel anti-Alzheimer's disease leading compounds targeting acetylcholinesterase, N-methyl-D-aspartic acid receptor, γ-secretase, peroxisome proliferator-activated receptor-γ and amyloid-β.