Jm. Roch et al., INCREASE OF SYNAPTIC DENSITY AND MEMORY RETENTION BY A PEPTIDE REPRESENTING THE TROPHIC DOMAIN OF THE AMYLOID BETA A4 PROTEIN-PRECURSOR/, Proceedings of the National Academy of Sciences of the United Statesof America, 91(16), 1994, pp. 7450-7454
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.