THE AMYLOID PRECURSOR PROTEIN OF ALZHEIMERS-DISEASE IS FOUND ON THE SURFACE OF STATIC BUT NOT ACTIVELY MOTILE PORTIONS OF NEURITES

We have previously found that the amyloid precursor protein (APP) of A lzheimer's disease is present on the surface of rat cortical neurons i n culture, in a segmental pattern which first becomes evident after 24 hours and is fully developed by five days. As APP has previously been reported to have a short half-life in neuronal cell lines, and has be en shown to contain binding sites for various extracellular matrix com ponents within its extracellular domain, we hypothesized that APP woul d be associated with portions of neurites undergoing rapid structural change, such as growth cones. To test this hypothesis, we observed sel ected neurons by video time-lapse differential interference microscopy on 24-hour-old primary rat neuronal cultures for up to 45 minutes, fo llowed by fixation and immunocytochemistry to ascertain surface APP di stribution on those same neurons. In contrast to our predictions, surf ace APP was not found on active portions of neurites, even if the acti vity produced no net translational movement. This result indicates tha t surface APP is actually associated with stable portions of neurites, a conclusion that tallies with other recent results showing that neur onal surface APP has a longer half-life than general cellular APP, and is associated with markers of adhesion patches, which themselves are relatively stable structures.