β-Amyloid precursor protein gene in squirrel monkeys with cerebral amyloid angiopathy

Abstract

Senescent nonhuman primates frequently develop cerebral β-amyloidosis; for reasons that are not yet understood, the primary histological locus of β-amyloid deposition varies in different species. In aged rhesus monkeys (Macaca mulatta), fibrillar (congophilic) β-amyloid (Aβ) occurs most frequently in senile plaques, whereas in aged squirrel monkeys (Saimiri sciureus) the cerebral blood vessels are most affected. To determine if cerebral β-amyloid angiopathy (CAA) in squirrel monkeys is related to a species-specific amino acid change in Aβ, as was shown in two hereditary human forms of CAA, the β-amyloid precursor protein (βPP₇₅₁) cDNA was sequenced. The predicted amino acid sequence of Aβ in squirrel monkeys is identical to that in normal humans. Overall, βPP₇₅₁ in the squirrel monkey differs from the human sequence only by four amino acids near the N-terminus and in the KPI domain. These findings suggest that other factors most likely predispose aged squirrel monkeys to cerebral amyloid angiopathy. We propose the squirrel monkey as a useful model for studying the factors contributing to human CAA, and for testing diagnostic and therapeutic approaches to this disorder.