MEMORY-ENHANCING EFFECTS OF SECRETED FORMS OF THE BETA-AMYLOID PRECURSOR PROTEIN IN NORMAL AND AMNESTIC MICE

When administered intracerebroventricularly to mice performing various learning tasks involving either short-term or long-term memory, secre ted forms of the beta-amyloid precursor protein (APP(751)(s) and APP(6 95)(s)) have potent memory enhancing effects and block learning defici ts induced by scopolamine. The memory-enhancing effects of APP(s) were observed over a wide range of extremely low doses (0.05-5,000 pg intr acerebroventricularly), blocked by anti-APP(s) antisera, and observed when APP(s) was administered either after the first training session i n a visual discrimination or a lever-press learning task or before the acquisition trial in an object recognition task APP(s) had no effect on motor performance or exploratory activity. APP(695)(s) and APP(751) (s) were equally effective in the object recognition task, suggesting that the memory-enhancing effect of APP(s) does not require the Kunitz protease inhibitor domain. These data suggest an important role for A PP(s)s on memory processes.