Synthetic amyloid-β oligomers drive early pathological progression of Alzheimer's disease in nonhuman primates

As an insidious and slowly progressive neurodegenerative disorder, Alzheimer's disease (AD) uniquely develops in humans but fails in other species. Therefore, it has been challenged to rebuild human AD in animals, including in non-human primates. Here, we bilaterally delivered synthetic A beta oligomers (A beta Os) into the cerebral parenchyma of cynomolgus monkeys, which rapidly drove the formation of massive A beta plaques and concomitant neurofibrillary tangles in the cynomolgus brain. The amyloid and tau pathology as well as their co-occurrence in A beta O-monkeys were reminiscent of those in patients with AD. In addition, the activated astrocytes and microglia surrounding A beta plaques indicated the triggered neuroinflammation. The degenerative neurons and synapses around A beta plaques also emerged in cynomolgus brain. Together, soluble A beta Os caused the cascade of pathologic events associated with AD in monkeys as occurred in patients at the early phase, which could facilitate the development of a promising animal model for human AD in non-human primates.