Amyloid beta-protein induces the cerebrovascular cellular pathology of Alzheimer's disease and related disorders.
One of the hallmark pathologic characteristics of Alzheimer's disease (AD) and related disorders is deposition of the 39-42 amino acid amyloid beta-protein (A beta) in the walls of cerebral blood vessels. The cerebrovascular A beta deposits in these disorders are associated with degenerating smooth muscle cells in the vessel wall which have been implicated in the expression of the amyloid beta-protein precursor (A beta PP) and formation of A beta. We have established primary cultures of human cerebrovascular smooth muscle cells as a model for investigating the cellular pathologic processes involved in the cerebral amyloid angiopathy of AD and related disorders. Recently, we have shown that A beta 1-42, the predominant pathologic cerebrovascular form of A beta, causes extensive cellular degeneration that is accompanied by a striking increase in the levels of cellular A beta PP, potentially amyloidogenic carboxyl terminal A beta PP fragments, and soluble A beta peptide in the cultured human cerebrovascular smooth muscle cells. Together, these studies provide evidence that A beta contributes to the onset and progression of the cerebrovascular pathology associated with AD and related disorders and suggests the mechanism involves a molecular cascade with a novel product-precursor relationship that results in the adverse production and accumulation of A beta.
Van Nostrand
W E
WE
Department of Microbiology, College of Medicine, University of California, Irvine 92717-4025, USA.
Davis-Salinas
J
J
Saporito-Irwin
S M
SM
D000544:Alzheimer Disease / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000494:pharmacology*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D001921:Brain / Q000098:blood supply* / Q000187:drug effects; D016657:Cerebral Amyloid Angiopathy / Q000378:metabolism; D002536:Cerebral Arteries / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D002550:Cerebral Veins / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008578:Meninges / Q000098:blood supply; D008955:Models, Cardiovascular; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009410:Nerve Degeneration; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology; D012995:Solubility
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments