BEHAVIORAL AND NEUROPATHOLOGIC CHANGES INDUCED BY CENTRAL INJECTION OF CARBOXYL-TERMINAL FRAGMENT OF BETA-AMYLOID PRECURSOR PROTEIN IN MICE

Expression of the carboxyl-terminal fragment (CT) of the beta-amyloid precursor protein (APP) in transgenic animals has been linked with neu rotoxicity. However, it remains to be clarified whether the neurotoxic ity is caused by beta-amyloid proteins (A beta s) derived from CT or b y CT itself. To study the in vivo neurotoxicity of CT, mice were given a single intracerebroventricular injection of a recombinant 105-amino acid CT (CT105; 68.5-685 pmol, intracerebroventricularly), and change s in behavior and in brain histology were examined. Animals given CT10 5 (410 or 685 pmol, intracerebroventricularly) showed a dose-dependent impairment in the passive avoidance performance, whereas boiled CT105 had no effect. CT105 (685 pmol, intracerebroventricularly) induced re active gliosis in neocortex and hippocampus and neurodegeneration in n eocortex. These results indicate that centrally administered CT105 ind uces behavioral impairment and neuropathologic changes, suggesting a d irect toxic effect of CT105 per se.