The stability of beta-amyloid precursor protein in nine different cell types.

Cell extracts from HeLa, macrophage, glial, C6, PC12, IMR-32, neuroblastoma, CHP-100 and P19 cells were examined for APP and its different derivatives by immunoblotting. When five antibodies (raised against different parts of APP) were used to stain western blots of nine cell extracts, three groups of immunoreactive proteins were observed: high molecular weight-(HMW, 70-125 kDa), medium molecular weight-(MMW, 30-40 kDa) and low molecular weight (LMW, 4-16 kDa). The intensity of immunoreactivity among these three groups of proteins varied in each cell line. The strongest signal for HMW protein was observed in PC 12 cells, the strongest signal for MMW protein was observed in C6 astrocyte cells, and both HMW and MMW protein bands were detected in macrophages and P19 cell lines. LMW protein bands could be detected only by antibody against the carboxyl-terminal part of the APP molecule. These experiments suggest that APP is processed differently in the various cell types. The conversion of APP to beta-peptide may be related to the stability of APP in cells and the understanding of these intermediate steps of APP processing is crucial to the elucidation of Alzheimer's disease.