During the performance of this study Dr. M. M. Verbeek was a visiting scientist at the Department of Microbiology and Molecular Genetics, University of California, Irvine, CA, U.S.A.
Rapid Degeneration of Cultured Human Brain Pericytes by Amyloid β Protein
Article first published online: 18 NOV 2002
Journal of Neurochemistry
Volume 68, Issue 3, pages 1135–1141, March 1997
How to Cite
Verbeek, M. M., De Waal, R. M. W., Schipper, J. J. and Van Nostrand, W. E. (1997), Rapid Degeneration of Cultured Human Brain Pericytes by Amyloid β Protein. Journal of Neurochemistry, 68: 1135–1141. doi: 10.1046/j.1471-4159.1997.68031135.x
- Issue published online: 18 NOV 2002
- Article first published online: 18 NOV 2002
- Received July 12, 1996; revised manuscript received October 21, 1996; accepted October 23, 1996.
- Alzheimer's disease;
- Amyloid β protein;
- Smooth muscle cells
Abstract: Amyloid β protein (Aβ) 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 Aβ deposition is accompanied by degeneration of smooth muscle cells and pericytes. In this study we found that Aβ1–40 carrying the “Dutch” mutation (HCHWA-D Aβ1–40) as well as wild-type Aβ1–42 induced degeneration of cultured human brain pericytes and human leptomeningeal smooth muscle cells, whereas wild-type Aβ1–40 and HCHWA-D Aβ1–42 were inactive. Cultured brain pericytes appeared to be much more vulnerable to Aβ-induced degeneration than leptomeningeal smooth muscle cells, because in brain pericyte cultures cell viability already decreased after 2 days of exposure to HCHWA-D Aβ1–40, 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 Aβ1–40. 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 Aβ is crucial for initiating its destructive effects. These data imply an important role for Aβ in inducing perivascular cell pathology as observed in the cerebral vasculature of patients with Alzheimer's disease or HCHWA-D.