Mary Ann Liebert, Inc. Publishers
Faculty of Computing, Health and Science
School of Exercise, Biomedical and Health Science / Centre of Excellence for Alzheimer's Disease Research and Care
Reliable animal models are required to facilitate the understanding of neurodegenerative pathways in Alzheimer’s disease. Animal models can also be employed to search for disease-modifying drugs. The embryos and larvae of zebrafish are particularly advantageous for this purpose. For Alzheimer’s disease, drugs that can ameliorate amyloidb (Ab) toxicity have therapeutic and=or prophylactic potential. We attempted to generate a zebrafish model of Ab toxicity that would be viable and fertile but have a highly visible pigmentation phenotype in larvae. The larvae could then be arrayed in microtiter plates to screen compound libraries for drugs acting to reduce Ab toxicity. We used the promoter of the zebrafish mitfa (nacre) gene to drive expression of the pathological 42 amino acid species of human Ab, Ab42, specifically in the highly visible melanophores (melanocytes) of transgenic zebrafish. However, the transgenic fish only showed an aberrant pigment phenotype in adults at the advanced age of 16 months. Nevertheless, our results show that alteration of zebrafish pigment pattern may be useful for analysis of toxic peptide action.