Primate-like amyloid-β sequence but no cerebral amyloidosis in aged tree shrews

A central pathological feature of Alzheimer’s disease is the profuse deposition of amyloid-β protein (Aβ) in the brain parenchyma and vessel walls. Aβ also forms deposits in the brains of a variety of mammals, including all aged non-human primates studied to date. The sequence of Aβ in these animals is identical to that in humans. No Aβ deposits have been found in the brains of wild-type rats and mice, suggesting that the three amino acid differences between their Aβ and that of amyloid-bearing mammals impedes the fibrillogenicity of Aβ. Analysis of the primary sequence of the β-amyloid precursor protein in tree shrews revealed a 98% similarity and 97% identity with the human protein. Furthermore, the predicted amino acid sequence of Aβ in tree shrews is identical to that in humans. However, immunohistochemical analysis failed to reveal β-amyloid deposits in the neural parenchyma or vasculature of eight aged (7–8 years) tree shrews (Tupaia belangeri). The lack of correlation between the Aβ sequence and amyloid formation suggests that other factors contribute to cerebral amyloid deposition in aged animals.