Alzheimer’s disease (AD), the most common cause of dementia in the elderly, is a complex
neurodegenerative disorder that frequently results in a progressive decline in cognitive functions.
Many in vitro and in vivo studies have shown that multiple factors, including low acetylcholine levels,
metal dyshomeostasis, oxidative stress, and A (amyloid-) aggregation, may play a role in the
development of Alzheimer’s disease. However, the pathogenesis of Alzheimer’s disease is still
unknown. To screen anti-AD drugs, experimental animal models that mimic AD pathological
processes are required. For a long time, mice were the dominant model for studying Alzheimer’s
disease. Zebrafish models have received a lot of attention in recent years and are widely used due to
their low cost. Paquet et al., for example, created a tau transgenic zebrafish model to identify
compounds that target tau phosphorylation. Inhibiting GSK3, a potential AD drug target, resulted in a
headless zebrafish embryo, which was used to successfully identify several GSK3 inhibitors.
However, because most zebrafish models of Alzheimer’s disease are transgenic, which is both
expensive and time-consuming, a new zebrafish model for rapid screening of anti-AD drugs is in high
demand.
Zebrafish are an excellent model for genetic and molecular research. By injecting morpholino
antisense oligonucleotides, mRNA, transgenes, and, more recently, genome engineering systems,
zebrafish embryos can be genetically manipulated. These technologies have the ability to make both
subtle and drastic changes in gene expression, which can be seen in developing transparent embryos.
Morpholinos are proteins that are designed to bind to specific sites in transcripts from a gene of
interest. A morpholino can either block mRNA translation (knockdown) or interfere with correct exon
splicing. Injection of sense mRNA can result in the overexpression of a specific gene of interest. In
general, the effects of morpholino and mRNA injection last only during embryogenesis (2–3 days
after fertilisation). Transgenic zebrafish can be created by inserting genes controlled by tissue-specific
promoters using efficient vectors such as the Tol2 transposase system. The Cre/loxP and GAL4-UAS
systems can also be used to generate conditionally expressed transgenics for gene function analysis at
specific time points. The lack of available technology to generate targeted mutations in the zebrafish
genome was previously a disadvantage of the zebrafish model in comparison to rodents.
The zebrafish is quickly becoming a popular model for Alzheimer’s disease research. They are an
excellent model for drug testing prior to rodent clinical trials. However, there are still some aspects of
this model that need to be better understood. To use the zebrafish system to model aspects of AD
pathobiology, we must first better understand zebrafish brain structure and function, as well as adult
zebrafish brain physiology. So far, research has revealed that the zebrafish brain has a reasonable
level of basic structure conservation when compared to mammals, as well as neuroanatomical and
neurochemical pathways that are similar to those involved in human disease. Using the zebrafish, we
were able to observe and analyse aspects of presenilin gene biology that would have been difficult to
observe/analyze in other models. However, in order to effectively analyse future transgenic and
mutant zebrafish models of AD, we need to improve our understanding of the functions in zebrafish
of some of the key genes implicated in human AD pathogenesis, such as MAPT and APOE. It is
debatable whether zebrafish can be used to model a late-onset disease like Alzheimer’s because
zebrafish have a high capacity for regeneration, which must have an impact on the development of
neurodegenerative phenotypes. Neurogenesis is much more abundant in the adult zebrafish brain than
in mammals, making analysis of neuronal loss difficult. Despite these constraints, the recent
availability and feasibility of genome editing technologies presents an exciting opportunity to develop
zebrafish genetic models of neurodegenerative diseases such as Alzheimer’s disease.FAD mutations
will inevitably be introduced into zebrafish FAD gene orthologs.Animal models can be used to study
the causes and pathologies of human diseases.

Obviously, such models can never capture the full pathology seen in human cases.Because of the
complexity of the human brain, Alzheimer’s disease is a particularly difficult disease to model in
animals. However, by employing a variety of models, including the zebrafish, we can exploit the
distinct characteristics of each to uncover the molecular basis of this disease.