Memory-enhancing effects of secreted forms of the β-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, secreted forms of the β-amyloid precursor protein (APP(s)₇₅₁ and APP(s)₆₉₅) have potent memory-enhancing effects and block learning deficits 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 intracerebroventricularly), blocked by antiAPP(s) antisera, and observed when APP(s) was administered either after the first training session in 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(s)₆₉₅ and Apps(s)₇₅₁ 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 APP(s)s on memory processes.