beta-Amyloid precursor protein gene in squirrel monkeys with cerebral amyloid angiopathy.
Senescent nonhuman primates frequently develop cerebral beta-amyloidosis; for reasons that are not yet understood, the primary histological locus of beta-amyloid deposition varies in different species. In aged rhesus monkeys (Macaca mulatta), fibrillar (congophilic) beta-amyloid (A beta) occurs most frequently in senile plaques, whereas in aged squirrel monkeys (Saimiri sciureus) the cerebral blood vessels are most affected. To determine if cerebral beta-amyloid angiopathy (CAA) in squirrel monkeys is related to a species-specific amino acid change in A beta, as was shown in two hereditary human forms of CAA, the beta-amyloid precursor protein (beta PP) cDNA was sequenced. The predicted amino acid sequence of A beta in squirrel monkeys is identical to that in normal humans. Overall, beta PP751 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.
Department of Pharmacology, New York University Medical Center, NY 10016, USA.
E
E
Levy
A
A
Amorim
B
B
Frangione
L C
LC
Walker
D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D016657:Cerebral Amyloid Angiopathy / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000032:analysis; D005796:Genes; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012453:Saimiri; D012689:Sequence Homology, Nucleic Acid
D016564:Amyloid beta-Protein Precursor; D004247:DNA