Alzheimer β-amyloid precursor proteins display specific patterns of expression during embryogenesis

The beta-amyloid precursor proteins (beta APPs) are a family of glycosylated transmembrane proteins that include in their sequences the beta-amyloid peptide, a major component of the characteristic amyloid deposits or senile plaques found in the brains of Alzheimer's disease patients and aged Down's syndrome subjects. Various beta APP isoforms, mainly beta APP-695, beta APP-714, beta APP-751 and beta APP-770, the number corresponding to the number of amino acids they encode, resulting from the alternative splicing of a single primary transcript have been described. Using oligonucleotides recognizing each of the four major Alzheimer's beta APP mRNAs, we have found that each beta APP mRNA displays a specific temporal and spatial pattern of expression. The prototype isoform beta APP-695 occurs early in cells actively implicated in morphogenetic events, as those mesodermal cells invaginating at the level of the primitive streak, and it is later restricted to the neurectodermal (neural tube, neural crest and neurogenic placode) derivatives. By contrast, the longest isoform beta APP-770 appears later and restricted to mesodermal and endodermal derivatives. The isoforms beta APP-714 and beta APP-751;ve still expressed later than the other two isoforms and distributed ubiquitously, though beta APP-714 transcripts predominate typically within the neural tube. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.