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 angiopath y (CAA). The normal leptomeningeal smooth muscle cells and CAA/ leptom eningeal smooth muscle cells were compared to normal human aorta smoot h muscle cells with respect to amyloid beta-protein precursor (A beta PP) expression. All the cultured smooth muscle cells secreted a promin ent 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 cel ls secrete approximate to 1.5-fold more PN-2/ABPP than normal leptomen ingeal smooth muscle cells and CAA/ leptomeningeal smooth muscle cells . In contrast the normal leptomeningeal smooth muscle cells and CAA/ l eptomeningeal smooth muscle cells retain approximate to 2.4- and appro ximate 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 smoo th muscle cells compared to aorta smooth muscle cells may contribute t o the formation of AP that is selectively deposited in the waifs of co rtical and leptomeningeal blood vessels.