Ontogenetic changes in protein level of amyloid precursor protein (APP) ingrowth cones and synaptosomes from rat brain and prenatal expression pattern of APP mRNA isoforms in developing rat embryo

To elucidate the functional role of the amyloid precursor protein (APP) dur ing brain ontogeny, developmental changes of APP levels in growth cones and synaptosomes were studied from embryonic day 14 up to postnatal day (PD) 4 00 using Western analysis. APP level in growth cones was low during prenata l stages of development, but demonstrating a continuous increase from PD 3 up to PD 10. Highest concentration of APP in synaptosomes was found between PD 7 and 10, followed by a considerable decrease up to PD 30 and persistin g at this level up to PD 400. In situ hybridization to differentiate betwee n APP695 mRNA, APP751 mRNA and APP770 mRNA revealed distinct age-related ex pression pattern of various APP isoforms. During prenatal brain development APP695 mRNA is maximally expressed in brain structures, containing differe ntiating nerve cells. APP751 and APP770 mRNA isoforms are diffusely distrib uted in the embryo throughout the prenatal period examined and their expres sion is higher in peripheral organs such as skin, lung, liver and bones as compared to the brain. The increase of APP level during synaptogenesis sugg ests a functional role of APP in the processes of neurite outgrowth and cel l targeting as well as in the maintenance of the functional integrity of sy napses in the mature brain. The APP695 isoform seems to be the major form i nvolved in embryonic brain maturation. (C) 2001 ISDN. Published by Elsevier Science Ltd. All rights reserved.