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 Alzheimer's disease brains. Although definite proof is still lacking, it is very well possible that the amyloid and its associated proteins are produced locally in the brain. In this paper we describe the development of a model system of cultured human brain pericytes to study the mechanisms of microvascular amyloid formation in vitro. These cultured cells may serve to study several aspects of cerebrovascular amyloidosis, which include the production of the amyloid precursor protein and of amyloid beta-protein-associated proteins as well as cytotoxic effects of amyloid beta-protein on perivascular cells. We demonstrated that pericytes produce and metabolize the amyloid precursor protein, and that they produce amyloid beta-protein-associated proteins, such as heparan sulfate proteoglycans, apolipoprotein E, and complement factor C1q. 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 important mechanism to explain the cell death observed in vivo. Our data indicate that this cell culture model of human brain pericytes provides a useful and pathophysiologically relevant tool to study cerebrovascular amyloidosis.
Verbeek
M M
MM
Department of Pathology, University Hospital Nijmegen, The Netherlands. m.verbeek@pathol.azn.nl
Otte-Höller
I
I
Ruiter
D J
DJ
de Waal
R M
RM
D000544:Alzheimer Disease / Q000209:etiology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000686:Amyloidosis / Q000209:etiology*; D001053:Apolipoproteins / Q000378:metabolism; D015153:Blotting, Western; D001921:Brain / Q000098:blood supply / Q000378:metabolism*; D002470:Cell Survival; D002478:Cells, Cultured; D002561:Cerebrovascular Disorders / Q000209:etiology*; D002918:Chymotrypsin / Q000037:antagonists & inhibitors; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D020286:Pericytes / Q000378:metabolism*; D013997:Time Factors
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D001053:Apolipoproteins; D019812:Heparan Sulfate Proteoglycans; D002918:Chymotrypsin