Involvement of amyloid precursor protein in memory formation in the rat: an indirect antibody approach

The potential role of different isoforms of amyloid precursor proteins (APPs) in memory and learning processes was investigated in rats using antibodies differentiating between APP isoforms containing or lacking the Kunitz protease inhibitor (KPI) domain. Rats received intracerebroventricular injection of control immunoglobulins (IgGs), anti-KPI-APP (= anti-P3) or anti-N-terminus-APP (= anti-P4). No immediate effects on learning of a passive avoidance task were observed; however, performance evaluated 1 day later was somewhat impaired by the anti-P3 antibody (reacting with APP_KPI) and even more markedly impaired by the anti-P4 antibody (reacting with both APP₆₉₅ and APP_KPI) relative to control antibody. The antibodies did not affect performance of an active avoidance task acquired prior to the experimental treatment or active avoidance learning 8 days post-treatment. These results suggest that blockade of APP by an antibody injected intracerebroventricularly impairs the consolidation and/or retrieval of memory in rats.