Advances in non-human primate models for Alzheimer's disease research

Abstract

Alzheimer’s disease (AD) is the most common progressive neurodegenerative disease. It is characterized by cognitive decline and brain pathology, including amyloid-β (Aβ) plaques, neurofibrillary tangles, and neuroinflammation. While rodent models have contributed to our understanding of a multiplicity of disease mechanisms, their limitations in replicating human age-related neurodegenerative diseases pose challenges for translating research findings to the clinical setting. The common marmoset (Callithrix jacchus), a small non-human primate, has emerged as a promising model for neuroscience and aging research. Age-related Aβ and tau pathologies develop naturally in the marmoset, which also possess a brain network organization, including a default mode network, that closely resembles that of humans. AD-related pathologies have also been experimentally induced in marmosets through injection of materials extracted from post-mortem brain tissue of AD patients. Recent advances in genome-editing technologies have enabled the development of marmoset models carrying familial AD mutations. These models offer new opportunities to investigate early pathological changes in the disease and to evaluate potential therapeutic agents. Taken together, these findings highlight the value of the marmoset as a translational model bridging the gap between rodent studies and human AD research.