Article

Rapid degeneration of cultured human brain pericytes by amyloid beta protein.

Department of Pathology, University Hospital Nijmegen, The Netherlands.
Journal of Neurochemistry (impact factor: 4.06). 04/1997; 68(3):1135-41. pp.1135-41
Source: PubMed

ABSTRACT Amyloid beta protein (A beta) deposition in the cerebral arterial and capillary walls is one of the major characteristics of brains from patients with Alzheimer's disease and hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D). Vascular A beta deposition is accompanied by degeneration of smooth muscle cells and pericytes. In this study we found that A beta 1-40 carrying the "Dutch" mutation (HCHWA-D A beta 1-40) as well as wild-type A beta 1-42 induced degeneration of cultured human brain pericytes and human leptomeningeal smooth muscle cells, whereas wild-type A beta 1-40 and HCHWA-D A beta 1-42 were inactive. Cultured brain pericytes appeared to be much more vulnerable to A beta-induced degeneration than leptomeningeal smooth muscle cells, because in brain pericyte cultures cell viability already decreased after 2 days of exposure to HCHWA-D A beta 1-40, whereas in leptomeningeal smooth muscle cell cultures cell death was prominent only after 4-5 days. Moreover, leptomeningeal smooth muscle cell cultures were better able to recover than brain pericyte cultures after short-term treatment with HCHWA-D A beta 1-40. Degeneration of either cell type was preceded by an increased production of cellular amyloid precursor protein. Both cell death and amyloid precursor protein production could be inhibited by the amyloid-binding dye Congo red, suggesting that fibril assembly of A beta is crucial for initiating its destructive effects. These data imply an important role for A beta in inducing perivascular cell pathology as observed in the cerebral vasculature of patients with Alzheimer's disease or HCHWA-D.

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Keywords

Alzheimer's disease
 
Amyloid beta protein
 
amyloid precursor protein production
 
amyloid-binding dye Congo red
 
beta 1-42 induced degeneration
 
beta-induced degeneration
 
brain pericyte cultures
 
cell death
 
cellular amyloid precursor protein
 
cerebral arterial
 
Cultured brain pericytes
 
cultured human brain pericytes
 
hereditary cerebral hemorrhage
 
increased production
 
inducing perivascular cell pathology
 
leptomeningeal smooth muscle cell cultures
 
leptomeningeal smooth muscle cell cultures cell death
 
leptomeningeal smooth muscle cells
 
major characteristics
 
smooth muscle cells