Individual isoforms of the amyloid beta precursor protein demonstrate differential adhesive potentials to constituents of the extracellular matrix.

The amyloid beta precursor protein (AbetaPP) can exist as a membrane-bound glycoprotein which modulates neural cell adhesion. The adhesion of clones of the AtT20 mouse pituitary cell line, transfected with cDNA coding for the 695 (AbetaPP695) and 751 (AbetaPP751) amino acid forms of the protein, to individual components of the extracellular matrix was determined using a centrifugal shear assay. On laminin, poly-L-lysine, fibronectin, and uncoated glass substrata, the cells transfected with AbetaPP695 (6A1 cells) demonstrated a 50% increase in adhesivity over nontransfected cells, while those transfected with AbetaPP751 (7A1 cells) showed a significant decrease in adhesion. There was, however, a significant increase in the adhesive strength of the 7A1 cells to collagen type IV with no change in the adhesivity of the 6A1 cells when compared with control. These changes in adhesivity could be attributed to changes in the levels of the membrane-bound protein and were not due to the interaction of soluble AbetaPP with elements of the extracellular matrix. These studies provide evidence for differential adhesivities of the constituent AbetaPP isoforms and the possible role of the Kunitz protease inhibitor (KPI) domain in influencing the adhesive properties of the protein backbone.