title: Amyloid beta-protein induces its own production in cultured degenerating cerebrovascular smooth muscle cells.
abstract: The progression of Alzheimer's disease and related disorders involves amyloid beta-protein (A beta) deposition and pathologic changes in the parenchyma as well as 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 shown to express the A beta precursor (A beta PP) and A beta. Here, we show that A beta 1-42, an abundant cerebrovascular form of A beta, causes cellular degeneration in cultured human cerebrovascular smooth muscle cells. This stress response is accompanied by a striking increase in the levels of cellular A beta PP and soluble A beta peptide produced in these degenerating cells. These data provide the first experimental evidence that A beta can potentially contribute to the onset and progression of the cerebrovascular pathology. The present findings suggest that this mechanism may involve a molecular cascade with a novel product-precursor relationship that results in the adverse production and subsequent accumulation of A beta.
authors.affiliation: Department of Microbiology and Molecular Genetics, University of California, Irvine 92717-4025, USA.
authors.forename: J
authors.initials: J
authors.lastname: Davis-Salinas
authors.forename: S M
authors.initials: SM
authors.lastname: Saporito-Irwin
authors.forename: C W
authors.initials: CW
authors.lastname: Cotman
authors.forename: W E
authors.initials: WE
authors.lastname: Van Nostrand
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000494:pharmacology / Q000502:physiology*; D002478:Cells, Cultured; D002560:Cerebrovascular Circulation / Q000187:drug effects; D006801:Humans; D015151:Immunoblotting; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology; D011233:Precipitin Tests
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments