The amyloid precursor protein of Alzheimer's disease is found on the surface of static but not activity motile portions of neurites.
We have previously found that the amyloid precursor protein (APP) of Alzheimer's disease is present on the surface of rat cortical neurons in 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 been shown to contain binding sites for various extracellular matrix components within its extracellular domain, we hypothesized that APP would be associated with portions of neurites undergoing rapid structural change, such as growth cones. To test this hypothesis, we observed selected neurons by video time-lapse differential interference microscopy on 24-hour-old primary rat neuronal cultures for up to 45 minutes, followed by fixation and immunocytochemistry to ascertain surface APP distribution on those same neurons. In contrast to our predictions, surface APP was not found on active portions of neurites, even if the activity produced no net translational movement. This result indicates that surface APP is actually associated with stable portions of neurites, a conclusion that tallies with other recent results showing that neuronal 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.
Department of Pathology, University of Melbourne, Parkville, Victoria, Australia.
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Storey
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Spurck
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Pickett-Heaps
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Beyreuther
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Masters
D016564:Amyloid beta-Protein Precursor / Q000032:analysis* / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal; D000954:Antigens, Surface / Q000032:analysis; D002465:Cell Movement; D048429:Cell Size; D002478:Cells, Cultured / Q000737:chemistry / Q000166:cytology / Q000648:ultrastructure; D007150:Immunohistochemistry; D018715:Microscopy, Video; D016501:Neurites / Q000737:chemistry* / Q000502:physiology; D009474:Neurons / Q000737:chemistry / Q000166:cytology / Q000648:ultrastructure; D010590:Phalloidine; D051381:Rats; D017207:Rats, Sprague-Dawley
D016564:Amyloid beta-Protein Precursor; D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D010590:Phalloidine