Table 5.

In vivo AD models in non-mammal species.

Non-Mammalian AD Models
Models	Model Type	Advantages	Pitfalls	References
Caenorhabditis elegans	Transgenic	Small, easy to breed, lots of progenies. Characterized nervous system, short lifespan. Sequenced genome. Transgenic C. elegans can express human hyperphosphorylated tau mutant or Aβ peptides and develop some AD features. Used to study molecular interactions and cellular pathways.	Do not naturally have Aβ and β-secretase, and so, do not have amyloid aggregates. Do not naturally have tau aggregates, either. Need to be used in combination with other models.	[165,166,170]
Drosophila melanogaster	Transgenic	Small, easy to breed. Characterized nervous system. Sequenced genome. Have AD-related genes. Behavioral tests. Availability of genetic tools to do transgenic or knockdown models. Used for high-throughput drug screening. Transgenic flies develop AD hallmarks, such as overexpression of amyloid peptides, amyloid aggregate formation, tau hyperphosphorylation, synaptic impairments, neurodegeneration, and reduction of memory and lifespan.	AD genes are not well-characterized. Homology with human proteins but not sufficient to naturally develop the disease. Need to do transgenic models, but they do not clearly recapitulate the disease. Need to be used in combination with other models such as mouse models. Invertebrate model is very different from human than all other vertebrate models.	[172,173,174,175,176,177]
Danio rerio (zebrafish)	Transgenic	Small, easy to breed, lots of progenies. Characterized nervous system. Entirely sequenced genome. Have AD-related genes. Behavioral tests. Used for high-throughput drug screening. Available genetic tools for transgenic or knockdown models.	AD genes are not all well-characterized. Homology with human proteins but not sufficient to naturally develop the disease. Need to do transgenic models. Lack of data due to its recent development.	[178,179,180]