SYNTHETIC AMYLOID BETA-PROTEIN FAILS TO PRODUCE SPECIFIC NEUROTOXICITY IN MONKEY CEREBRAL-CORTEX

Because progressive amyloid beta-protein (AbetaP) deposition and surrounding neuritic dystrophy occur spontaneously in primates, we evaluated the in vivo effects of synthetic AbetaP in monkey cortex. Experimental and control AbetaP were stereotactically injected into multiple neocortical sites of adult rhesus monkeys in a vehicle of either artificial cerebrospinal fluid or acetonitrile. After 2 weeks or 3 months, injection sites were identified and characterized histologically and immunocytochemically. AbetaP antibodies specifically detected the injected AbetaP1-40 peptide. Serial sections stained with silver and antineurofilament protein demonstrated comparable degrees of degenerating neurons, dystrophic neurites, and axonal spheroids associated with both experimental and control peptide injections. Alz 50 staining was sparse or absent in all sites. We conclude that specific cellular changes closely resembling AD pathology were not detected in these experiments, and that control and experimental AbetaP peptides produced indistinguishable effects. Methodological concerns regarding the in vivo modeling of AbetaP bioactivity are discussed.