Identification of different β amyloid cDNAs cloned from the brain of a patient with sporadic alzheimer's disease

Abstract

Neurofibrillary tangles and senile plaques, two neuropathological markers of Alzheimer's disease, may both contain peptide fragments derived from the β amyloid protein. Human β amyloid peptide precursor cDNAs have been isolated from normal foetal and adult brain libraries. In peripheral tissue and cultured cells, a novel precursor containing a protease inhibitor domain has been cloned. A cDNA library from the cerebral cortex of a patient with sporadic Alzheimer's disease was constructed and several clones coding for the β amyloid peptide precursor were isolated cDNAs containing two types of insertion coding for a serine protease inhibitor domain were identified. The use of another polyadenylation site available in the 3′-untranslated region of the mRNA was observed. These results indicate that, in one patient with Alzheimer's disease, different RNA species coding for the β amyloid peptide precursor arise by alternative splicing of a single transcriptional unit, and use different polyadenylation sites.