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Pathologic Amyloid β‐Protein Cell Surface Fibril Assembly on Cultured Human Cerebrovascular Smooth Muscle Cells
Author(s) -
Van Nostrand William E.,
Melchor Jerry P.,
Ruffini Lynda
Publication year - 1998
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1998.70010216.x
Subject(s) - fibril , thioflavin , congo red , chemistry , biophysics , amyloid (mycology) , amyloidosis , beta (programming language) , amyloid beta , circular dichroism , biochemistry , pathology , alzheimer's disease , biology , medicine , peptide , disease , inorganic chemistry , organic chemistry , adsorption , computer science , programming language
Cerebrovascular amyloid β‐protein (Aβ) deposition is a key pathological feature of Alzheimer's disease and hereditary cerebral hemorrhage with amyloidosis‐Dutch type (HCHWA‐D). Aβ 1–40 containing the E22Q HCHWA‐D mutation, but not wild‐type Aβ 1–40 , potently induces several pathologic responses in cultured human cerebrovascular smooth muscle cells, including cellular degeneration and a robust increase in the levels of cellular Aβ precursor. In the present study, we show by several quantitative criteria, including thioflavin T fluorescence binding, circular dichroism spectroscopy, and transmission electron microscopic analysis, that at a concentration of 25 µ M neither HCHWA‐D Aβ 1–40 nor wild‐type Aβ 1–40 appreciably assembles into β‐pleated sheet‐containing fibrils in solution over a 6‐day incubation period. In contrast, at the same concentrations, HCHWA‐D Aβ 1–40 , but not wild‐type Aβ 1–40 , selectively binds and assembles into abundant fibrils on the surfaces of cultured human cerebrovascular smooth muscle cells. The simultaneous addition of an equimolar concentration of the dye Congo red prevents the cell surface fibril assembly of HCHWA‐D Aβ 1–40 . Moreover, Congo red effectively blocks the key pathologic responses induced by HCHWA‐D Aβ 1–40 in these cells. The present findings suggest that the surface of human cerebrovascular smooth muscle cells may selectively orchestrate the assembly of pathogenic Aβ fibrils and that cell surface Aβ fibril formation plays an important role in causing the pathologic responses in these cells.