Abstract
Aged nonhuman primates accumulate large amounts of human-sequence amyloid β (Aβ) in the brain, yet they do not manifest the full phenotype of Alzheimer's disease (AD). To assess the biophysical properties of Aβ that might govern its pathogenic potential in humans and nonhuman primates, we incubated the benzothiazole imaging agent Pittsburgh Compound B (PIB) with cortical tissue homogenates from normal aged humans, humans with AD, and from aged squirrel monkeys, rhesus monkeys, and chimpanzees with cerebral Aβ-amyloidosis. Relative to humans with AD, high-affinity PIB binding is markedly reduced in cortical extracts from aged nonhuman primates containing levels of insoluble Aβ similar to those in AD. The high-affinity binding of PIB may be selective for a pathologic, human-specific conformation of multimeric Aβ, and thus could be a useful experimental tool for clarifying the unique predisposition of humans to Alzheimer's disease.