Cerebral Amyloid Angiopathy in Aged Dogs and Nonhuman Primates

Abstract

Cerebral amyloid angiopathy (CAA) is a common finding in aged dogs and nonhuman primates. As in humans, cerebrovascular amyloid in these animals is composed fundamentally of the Aβ peptide, along with various associated substances. The amount and distribution of CAA vary among brain regions and among animals of equivalent age. All vessel types can be involved, although amyloidotic venules are relatively rare. In nonhuman primates, capillaries are frequently affected; these small vessels accumulate almost exclusively the 42-amino acid peptide (Aβ42), whereas larger vessels contain a mix of Aβ42 and Aβ40. Compared to aged rhesus monkeys, which usually develop a preponderance of senile plaques, squirrel monkeys manifest mostly CAA. This species-difference is not due to differences in apolipoprotein E type or to known disease-causing polymorphisms in the β-amyloid precursor protein gene; however, squirrel monkeys have an Icelandic-like mutation in the cystatin C gene that could influence the tendency of these monkeys to accrue Aβ in the cerebral vasculature. Aged nonhuman primates and dogs are being used to test cerebral amyloid-targeting strategies and, along with emerging transgenic mice, are beneficial models for validating new diagnostic and therapeutic approaches to CAA.