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

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The β-amyloid precursor proteins (βAPPs) are a family of glycosylated transmembrane proteins that include in their sequences the β-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 βAPP isoforms, mainly βAPP-695, βAPP-714, βAPP-751 and βAPP-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 βAPP mRNAs, we have found that each βAPP mRNA displays a specific temporal and spatial pattern of expression. The prototype isoform βAPP-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 βAPP-770 appears later and restricted to mesodermal and endodermal derivatives. The isoforms βAPP-714 and βAPP-751 are still expressed later than the other two isoforms and distributed ubiquitously, though βAPP-714 transcripts predominate typically within the neural tube.