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

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.