AMYLOID PRECURSOR PROTEIN IN PERIPHERAL MONONUCLEAR-CELLS IS UP-REGULATED WITH CELL ACTIVATION

The deposition of beta/A4 protein in extraneural organs of patients wi th Alzheimer disease suggests that this peptide may in part be derived from a peripheral precursor. We studied expression of amyloid precurs or protein (APP) in PBMC. APP expression was detectable in resting PBM C by northern blot analysis, immunoblotting studies, and immunohistoch emistry. By reverse transcription-polymerase chain reaction, the 751 a nd 770 APP transcripts containing the Kunitz protease inhibitor (KPI) domain were approximately 10-fold more abundant than the 695 transcrip t lacking the KPI domain. Activation of PBMC with the lectin PHA-P was associated with an increase in apparent intracellular APP content by cytofluorometry, and an increase in the proportion of the 695 APP tran script lacking the KPI domain. We conclude that resting and activated PBMC express APP and could contribute to a circulating pool of this pr otein. In addition, PBMC APP is up-regulated with mitogenic stimulatio n and may participate in the regulation of activation of these cells.