Most neurodegenerative diseases are protein-misfolding disorders (PMDs), and animal models of PMDs are instrumental in addressing many important questions about their molecular pathogeneses and the development of therapeutic modalities. Hence, several model organisms have been utilized to generate animal models of PMDs. For example, Hart and colleagues expressed polyglutamine tracts in the ASH sensory neurons of Caenorhabditis elegans to model Huntington’s disease and found neurodegeneration and apoptosis of ASH neurons [37]. Zhong and colleagues expressed amyloid-β peptides Aβ42 in the neurons of Drosophila melanogaster and noted amyloid deposits, late-onset progressive neurodegeneration and olfactory learning defects [38]. Ayyagari and colleagues showed that a mutant allele of asparaginase like-1 (ASRGL1) identified in a family with inherited retinal degeneration induced protein aggregation in monkey kidney fibroblast-like COS-7 cells, and retinal photoreceptor degeneration in zebrafish larvae [39]. Hsiao and colleagues generated Tg2576 transgenic mice expressing a Swedish allele of amyloid precursor protein and observed impaired learning and memory and the deposition of amyloid plaques in the brain [19]. Although invertebrate model organisms such as C. elegans and D. melanogaster have been used to model PMDs, they have certain limitations. First, they lack key factors critical to many human PMD pathogeneses, such as myelination, specialized neuronal and glial cell types, and a sophisticated immune system. Second, the anatomical structures of their brains are quite divergent from those of humans [40]. On the other hand, zebrafish are vertebrates such that zebrafish can overcome aforementioned limitations. In addition, zebrafish present other advantages as a model of PMDs, such as small size, transparency, and external embryonic development. Thus, zebrafish can be used not only to investigate the molecular pathogenesis of PMDs, but also to develop therapeutics against PMDs. For example, inhibitors of polyglutamine protein aggregation were identified using zebrafish embryos [41]. As such, the zebrafish GFAP aggregation model we present here will help elucidate the molecular pathogenesis of AxD and serve as a basis for the development of AxD therapeutics.