CARBOXYL END-SPECIFIC MONOCLONAR ANTIBODIES TO AMYLOID-BETA PROTEIN (A-BETA) SUBTYPES (A-BETA-40 AND A-BETA-42(43)) DIFFERENTIATE A-BETA INSENILE PLAQUES AND AMYLOID ANGIOPATHY IN BRAINS OF AGED CYNOMOLGUS MONKEYS

Senile plaques (SPs) and cerebral amyloid angiopathy (CAA) in the brai ns of five aged (20-26 years old) cynomolgus monkeys were investigated immunohistochemically using two monoclonal antibodies (anti-A beta 40 (BA27) and anti-A beta 42(43) (BC05)) that can differentiate the carb oxyl termini of amyloid beta protein (A beta) subtypes. In four of fiv e animals, all types of SPs (i.e. diffuse, primitive, and classical pl aques; DPs, PPs, and CPs, respectively) were identified by BC05. Howev er, BA27 did not label DPs and stained only about one third of PPs and CPs, mainly labeling granular structures and cored portions, respecti vely. In CAA, lesions of cortical capillaries reacted to BC05 in four of five cases, but rarely and weakly to BA27 in two of five cases. On the other hand, lesions of parenchymal and meningeal arterioles were s tained by both BA27 and BC05. These staining profiles of SPs in cynomo lgus monkeys correspond well to those in humans, although there are tw o remarkable features in cynomolgus monkeys. First, BA27 stained PPs a ssociated with granular structures. Secondly, capillary A beta reacted intensely to BC05 but only slightly to BA27. Despite these unique fea tures, the results suggest that aged cynomolgus monkeys can be used to investigate the pathogenesis of A beta deposition in SPs and CAA.