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

A central pathological feature of Alzheimer's disease is the profuse deposi tion of amyloid-beta protein (A beta) in the brain parenchyma and vessel wa lls. A beta also forms deposits in the brains of a variety of mammals, incl uding all aged non-human primates studied to date. The sequence of A beta i n these animals is identical to that in humans. No A beta deposits have bee n found in the brains of wild-type rats and mice, suggesting that the three amino acid differences between their A beta and that of amyloid-bearing ma mmals impedes the fibrillogenicity of A beta. Analysis of the primary seque nce of the beta-amyloid precursor protein in tree shrews revealed a 98% sim ilarity and 97% identity with the human protein. Furthermore, the predicted amino acid sequence of A beta in tree shrews is identical to that in human s. However, immunohistochemical analysis failed to reveal beta-amyloid depo sits in the neural parenchyma or vasculature of eight aged (7-8 years) tree shrews (Tupaia belangeri). The lack of correlation between the A beta sequ ence and amyloid formation suggests that other factors contribute to cerebr al amyloid deposition in aged animals. (C) 1999 Elsevier Science Inc. All r ights reserved.