AMYLOID BETA-PROTEIN PRECURSOR IN CULTURED LEPTOMENINGEAL SMOOTH-MUSCLE CELLS

Smooth muscle cell cultures were established from human leptomeningeal blood vessels obtained at autopsy from a patient with normal cortical blood vessels and a patient with extensive cerebral amyloid angiopathy (CAA). The normal leptomeningeal smooth muscle cells and CAA/ leptomeningeal smooth muscle cells were compared to normal human aorta smooth muscle cells with respect to amyloid beta-protein precursor (A beta PP) expression. All the cultured smooth muscle cells secreted a prominent approximate to 110 kDa form of A beta PP that contained the Kunitz-type serine protease inhibitor domain analogous to protease nexin-2 (PN-2). Quantitative measurements revealed that aorta smooth muscle cells secrete approximate to 1.5-fold more PN-2/ABPP than normal leptomeningeal smooth muscle cells and CAA/ leptomeningeal smooth muscle cells. In contrast the normal leptomeningeal smooth muscle cells and CAA/ leptomeningeal smooth muscle cells retain approximate to 2.4- and approximate to 3.3-fold, respectively, more cell-associated A beta PP than aorta smooth muscle cells. These preliminary findings suggest that the decreased secretion of PN-2/A beta PP observed in leptomeningeal smooth muscle cells compared to aorta smooth muscle cells may contribute to the formation of AP that is selectively deposited in the waifs of cortical and leptomeningeal blood vessels.