Alzheimer’s disease (AD) is a complex neurodegenerative disorder that affects millions of
people worldwide. World Health Organization (WHO) indicate that by 2050, 150 million
persons, representing a 204% increase from 2017, will be living with dementia and the majority
of these increases will be found in Africa. There are various ways to study this condition and one of the first questions any researcher in this field grapples with is choosing the right model for Alzheimer’s Disease study

Maina et al., (2022) disclosed that most Africa neuroscience laboratories use wild-type rodents
such as mice and rats for their research. However, these are expensive to maintain and less
genetically amenable than many invertebrate and lover vertebrate model system. Other
animal models used in AD research are Drosophila, Zebrafish, Caenorhabditis elegans, Guinea
pig, and Monkey (Drummond & Wisniewski, 2017).

This review aims to outline the advantages and disadvantages of these models to serve as a guide in choosing the right model for Alzheimer’s Disease study.

Mice

Mice are the most commonly used animal model for AD research due to their genetic
similarity to humans and their relatively low cost. They have been used extensively to study
amyloid deposition and tau pathology. However, mice brain produces amyloid peptides distinct
from the human brain, thus AD in human are not well mimicked in mice or other rodents.

Drosophila

Drosophila has 70% of human disease-related genes in AD, short lifespan and ease
of genetic manipulation (Jucker, 2010). The orthologs found in the Drosophila genome AAPI has
30% similarity to human, thus providing profound insights into amyloid related toxins’ research.
However, Drosophila also does not develop all aspects of AD pathology seen in humans.

Zebrafish

This model has numerous advantages over mice, such as the optically transparent
embryo, rapid neurogenesis and swift manipulation of genetic makeup. However, limitations
include a higher mortality rate, difficulty in maintenance and lesser resemblance to human
physiology than rodents (Ansab et al., 2022).

Caenorhabditis elegans

C. elegans, a nematode which has 40% ortholog genes of APP and tau,
making it appropriate for the revelations of AD genomic-level research. This organism has the
advantages of needing less food and having observable neural structures, but it also has the
drawbacks of living for a short time and being difficult to manipulate due to its small size.

Guinea pig

Unlike mice, guinea pig has tau gene encoding isoforms with three microtubulebinding domain like human and also it is the only small animal model where PS2V generation
has been discovered. Human neuroblastoma cells exposed to hypoxia-induced oxidative stress
and brain with late-onset AD have been shown to express the PS2V transcript. Nevertheless, it is
a poor tools for behavioral study and its manipulation is time consuming.

Monkey

Some nonhuman primates can develop signs of AD during the aging process that are
comparable to human, such as neuropathy, change in cognitive and behavioral patterns, so they
are good model for normal aging and naturally occurring amyloid deposition and display
cognitive impairment. However, monkeys are expensive and ethically controversial (Ansab et
al., 2022).

What is the right model for Alzheimer’s disease study?

To sum up, none of the current AD models can fully capture the human AD pathology, but they
all have some aspect of it. These models have enabled some research advances and therapeutic
possibilities for clinical AD. Nevertheless to mimic global practice and to strengthen Africa’s
research landscape, small, low cost and genetically tractable model systems such as fruit flies,
zebrafish and C. elegans should be widely use for AD studies (Maina et al., 2020). With that being said, choosing the right model for Alzheimer’s Disease study will still depend largely on the research question at hand.

Reference

Ansab, A., Shraddha M., Shubham, D., Devendra K., Mohd. Farooq S. & Arvind N. (2022).
Preclinical models for alzheimer’s disease: Past, present, and future approaches. ACS Omega,
7 (51), 47504-47517.

Drummond, E. & Wisniewski, T. (2017). Alzheimer’s disease: experimental models and reality.
Acta Neuropathol, 133(2):155-175. doi: 10.1007/s00401-016-1662

Jucker, M. (2010). The benefits and limitations of animal models for translational research in
neurodegenerative diseases. Nat Med, 1210–1214. https://doi.org/10.1038/nm.2224

Maina, M. B., Hamidu, S. K., Ahmad, U., Abdulazeez, R., Muhammad, Z., Alkhamis, A. I.,
Umar, M. et al., (2022). Simple models for neuroscience research discoveries: How often are
these models used in africa. BioRxiv Preprint, 4, doi.org/ 10.1101/2022.12.30.522314

Maina, M. B., Hamidu, S. K., Ahmad, U, Ibrahim, H. A., Nasr, F. E., Salihu, A. T., Abushouk,
A. L. et al., (2020). 20 years of Africa neuroscience: Waking a sleeping giant. BioRxiv Preprint,
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