Pathogenic amyloid beta-protein induces apoptosis in cultured human cerebrovascular smooth muscle cells

The amyloid beta-protein (A beta) pathologically accumulates in cerebral va scular and senile plague deposits in the brains of patients with Alzheimer' s disease (AD) and related dis. orders including hereditary cerebral hemorr hage with amyloidosis Dutch type (HCMWA-D). The cerebrovascular deposits ar e accompanied by degeneration and eventual loss of smooth muscle cells in c erebral vessel wall. Similarly, we have shown that pathogenic forms of A be ta cause cell death in cultured human cerebrovascular smooth muscle (HCSM) cells in vitro. Here we show that pathogenic A beta induces a number of str uctural changes in HCSM cells Including shrinkage of cell bodies, retractio n of processes, disruption of the intracellular actin network, and nuclear condensation and fragmentation. These changes were accompanied by a number of biochemical alterations in the cells shown by in situ end labeling of nu clear DNA, proteolytic breakdown of smooth muscle cell a actin, and proteol ytic activation of the proteinase caspase 3. Together, these characteristic s are consistent with an apoptotic mechanism of cell death in HCSM cells in response to pathogenic A beta.