INCREASE OF SYNAPTIC DENSITY AND MEMORY RETENTION BY A PEPTIDE REPRESENTING THE TROPHIC DOMAIN OF THE AMYLOID BETA A4 PROTEIN-PRECURSOR/

The secreted form (sAPP) of the Alzheimer amyloid beta/A4 protein prec ursor (APP) has been shown to be involved in the in vitro regulation o f fibroblast growth and neurite extension from neuronal cells. The act ive site of sAPP responsible for these functions is within a small dom ain just C-terminal to the Kunitz-type protease inhibitor (KPI) insert ion site. We report here that a 17-mer peptide, containing this active domain of sAPP, can induce cellular and behavioral changes when infus ed into rat brains. After 2 weeks of APP 17-mer peptide infusion, the animals were tested for reversal learning and memory retention and wer e sacrificed for morphological examination of brains. We found that ad ministration of the APP 17-mer peptide resulted in an 18% increase in the number of presynaptic terminals in the frontoparietal cortex. At t he behavioral level, 17-mer-infused animals with nonimpaired learning capability showed an increased memory retention that seemed to interfe re with reversal learning performance. This APP 17-mer effect on memor y retention was not observed in animals with impaired initial learning capacity. These results suggest that APP is involved in memory retent ion through its effect on synaptic structure.