PRODUCTION OF AMYLOID-BETA-PEPTIDE BY CULTURED-CELLS - NO EVIDENCE FOR INTERNAL INITIATION OF TRANSLATION AT MET(596)

It has been suggested that the A beta fragment of the amyloid precursor protein in Alzheimer's disease arises from internal translation initiation at Met(596) (1). Here we use the recently described in vitro model of A beta production and secretion (2) to examine this hypothesis. We show that A beta is no longer detectable when the beta APP reading frame is destroyed by introduction of frame shift mutations that leave the A beta coding region intact. This result strongly suggests that internal initiation at Met(596) does not contribute significantly to the amount of A beta observed.