Modeling neurodegenerative diseases using non-human primates: advances and challenges

Abstract

Neurodegenerative diseases (NDs), such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS), are pathologically characterized by progressive loss of selective populations of neurons in the affected brain regions and clinically manifested by cognitive, motor, and psychological dysfunctions. Since aging is the major risk factor for NDs and the elderly population is expected to expand considerably in the coming decades, the prevalence of NDs will significantly increase, leading to a greater medical burden to society and affected families. Despite extensive research on NDs, no effective therapy is available for NDs, largely due to a lack of complete understanding of the pathogenesis of NDs. Although research on small animal and rodent models has provided tremendous knowledge of molecular mechanisms of disease pathogenesis, few translational successes have been reported in clinical trials. In particular, most genetically modified rodent models are unable to recapitulate striking and overt neurodegeneration seen in the patient brains. Non-human primates (NHPs) are the most relevant laboratory animals to humans, and recent studies using NHP neurodegeneration models have uncovered important pathological features of NDs. Here, we review the unique features of NHPs for modeling NDs and new insights into AD, PD, and ALS gained from animal models, highlight the contribution of gene editing techniques to establishing NHP models, and discuss the challenges of investigating NHP models.

Mammalian Models in Alzheimer’s Research: An Update

“…NHPs pose major similarities to the human brain than a mouse. Monkeys and humans share a similar morphology and composition of cell types [195,196]. NHPs are closely related to humans in many aspects like physiology, metabolism, the aging process, and genomic regulation.…”

“…NHPs are most suitable for determining behavioral abnormalities that occur in ND. NHPs make it easier to study certain phenotypes like depressive behavior or cognitive impairment in ND which is not possible in smaller animals [196,197]. Despite all the positive aspects of using NHP models for research, there are some limitations to it as well.…”

“…Age plays an important role when studying ND, so it can be assumed that these animals will show phenotype and neuropathology when they grow old. The cost of maintaining NHPs throughout their life span thus increases [196].…”