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Li. Ageing Neur Dis 2023;3:17 https://dx.doi.org/10.20517/and.2023.24 Page 3 of 4

the first genetic risk factor for Alzheimer’s disease (AD), which is present in primates but absent in rodents.
Non-human primate models are particularly valuable for studying behavioral abnormalities that are also
observed in NDs. Li et al. provided an overview of several non-human primate models used in ND
[5]
research . Among the recently established models, the monkey model with mutations in the PINK1 gene,
which cause early-onset Parkinson's disease (PD), offers unique insights into disease pathogenesis.
Knocking out the PINK1 gene in rodents and pigs failed to reproduce the severe phenotypes and
neurodegeneration observed in patients with PINK1 mutations. However, CRISPR-mediated PINK1 gene
[6]
mutations in monkeys result in severe neurodegeneration (Yang et al., 2019) . Further investigations of the
PINK1 mutant monkey model suggest that the loss of PINK1 causes neurodegeneration through a
[7]
mitochondria-independent mechanism (Yang et al., 2022) . Therefore, non-human primate models can
reveal important pathogenetic mechanisms that may not occur in small animals but are unique to primate
brains.

Although large animals possess many advantages for investigating NDs, there are challenges in widely
utilizing them in research. Scaling up studies on large animals is difficult due to the high cost of maintaining
them and the long reproduction and breeding periods. Despite recent advances in genetic editing tools,
establishing knock-in monkey models remains challenging. Additionally, behavioral and functional
assessments for large animal models are not as well-established as those for rodents. In the future, mouse
models will continue to be valuable and widely used in biomedical research. However, it is important to
consider large animal models as important alternatives to bridge the gap between small animals and
humans. They can help discover pathogenic events and mechanisms that may be specific to primates, and
more importantly, validate crucial therapeutic targets and effects.

DECLARATIONS
Authors’ contributions
The author contributed solely to the article.

Availability of data and materials
Not applicable.

Financial support and sponsorship
None.

Conflicts of interest
The author declared that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Copyright
© The Author(s) 2023.

REFERENCES
1. Novati A, Singer-mikosch E, Yu-taeger L, Clemensson E, Nguyen HP. Rat models of major neurodegenerative disorders. Ageing Neur
Dis 2022;2:17. DOI