Alzheimer-type tau pathology in advanced aged nonhuman primate brains harboring substantial amyloid deposition

Abstract

We elucidated how Alzheimer-type pathologies of amyloid beta-protein (Abeta) and tau spatiotemporally emerge in brains of nontransgenic nonhuman primate, cynomolgus monkey, in the present study. To examine the accumulation of deposited Abeta, phosphorylated tau accumulation, intracellular tau accumulation, and neurofibrillary tangle formation, the brains, mainly temporal cortex and hippocampus, of 34 cynomolgus monkeys aged 6 to 36 years were studied by biochemical and histochemical analyses. Biochemically, first, the accumulation of insoluble Abeta was detected in the neocortical (temporal and frontal) and hippocampal regions of animals as young as mid-20s and their levels were extremely high in those of advanced age. The accumulation of phosphorylated tau in the same regions occurred before the age of 20 with poor correlation to the levels of insoluble Abeta. Histologically, intraneuronal and intraoligodendroglial tau accumulation was observed in temporal cortex and hippocampus of animals before the age of 20. In an advanced aged 36-year-old individual, argyrophilic tangles and tau-accumulated dystrophic neurites were markedly observed in the medial temporal area contiguous to limbic structures. Notably, these tau pathologies also emerged, to a lesser extent, in the temporal cortices of advanced aged animals harboring significant amounts of insoluble Abeta. These results suggest that the cynomolgus monkey can be used to elucidate the age-dependent sequence of Abeta and tau pathologies.