African Green Monkeys Respond to Synthetic AB Oligomers with Persistent Alzheimers-like Activation

Wild African green monkeys (AGMs) offer a translational model for early Alzheimers biology, with physiology more similar to humans. We transiently exposed AGMs to synthetic AB oligomers and, 12 months later, profiled paired proteomes from whole CSF and a CSF subcompartment enriched for extracellular vesicles. Despite no overt cognitive decline, AGM proteomes showed persistent Alzheimers-like remodeling, particularly in vascular, inflammatory, and neuronal systems. Parallel analysis of the CSF subcompartment revealed proteins and pathways under-represented in bulk CSF, sharpening disease-relevant signals and candidate biomarkers. This systems-level, longitudinal study establishes AGMs as a powerful platform for liquid biopsy discovery and illuminates basic biology of molecular responses to soluble AB oligomers accompany and potentially protect against neurodegeneration.