Human brain pericytes as a model system to study the pathogenesis of cerebrovascular amyloidosis in Alzheimer's disease

Cerebrovascular amyloidosis belongs to the pathological hallmarks of Alzhei mer's disease brains. Although definite proof is still lacking, it is very well possible that the amyloid and its associated proteins are produced loc ally in the brain. In this paper we describe the development of a model sys tem of cultured human brain pericytes to study the mechanisms of microvascu lar amyloid formation in vitro. These cultured cells may serve to study sev eral aspects of cerebrovascular amyloidosis, which include the production o f the amyloid precursor protein and of amyloid beta-protein-associated prot eins as well as cytotoxic effects of amyloid beta-protein on perivascular c ells. We demonstrated that pericytes produce and metabolize the amyloid pre cursor protein, and that they produce amyloid beta-protein-associated prote ins, such as heparan sulfate proteoglycans, apolipoprotein E, and complemen t factor Clq. They are also prone to cellular degeneration after treatment with amyloid beta-protein, which is accompanied by increased expression of a number of amyloid beta-protein-associated proteins. This may be an import ant mechanism to explain the cell death observed in vivo. Our data indicate that this cell culture model of human brain pericytes provides a useful an d pathophysiologically relevant tool to study cerebrovascular amyloidosis.