Developmental spatiotemporal expression of Alzheimer beta APP isoforms in the chick embryo

The beta -amyloid precursor proteins (beta APPs) are a group of glycoprotei ns that result from the alternative splicing of a single primary transcript . They contain in their sequences the beta -amyloid peptide (beta A4), the principal component of the cerebral amyloid plaques found in patients with Alzheimer's disease. Using antibodies recognizing different regions of the major beta APPs,we have analysed by immunohistochemistry their spatiotempor al expression during chick embryogenesis. We have observed that the beta AP P isoforms containing the Kunitz protease inhibitor domain (beta APP-KPI) h ave a more widespread distribution than the isoforms lacking this domain. A lso, differential patterns of expression between both types of isoforms wer e detected in many embryonic tissues, including the floor and roof plates o f the neural tube, and sites of active axogenesis in the dorsal diencephalo n and mesencephalon. An antibody that recognizes the C-terminal sequence of beta A4 did not display immunoreaction until a relatively late phase of em bryogenesis, the 8 day of incubation. These observations suggest that the c hick embryo may be a simple and useful model for the analysis of beta APP p rocessing and function.