Studies of amyloid beta-protein precursor expression in Alzheimer's disease

The generation of the beta/A4 peptide and its accumulation into insoluble amyloid deposits represent key events in the neuropathologic process of Alzheimer's disease (AD). This posit has gained further support from recent reports that beta/A4 is directly responsible for the death of neurons. Potential therapies for AD aimed at abating the production of beta/A4 will require the basic knowledge of where it comes from. The 4.2-kD peptide is derived from a much larger amyloid precursor protein (APP) encoded by a gene that produces multiple transcripts. Employing in situ hybridization with biotinylated oligonucleotide probes, we set out to define which forms of the precursor are synthesized in affected regions of AD brain (e.g., hippocampal formation) and to determine the cell populations responsible for their manufacture.