Rapid Degeneration of Cultured Human Brain Pericytes by Amyloid β Protein

Authors

  • Marcel M. Verbeek,

    Corresponding author
    1. Department of Pathology, University Hospital Nijmegen, Nijmegen, The Netherlands;
      Address correspondence and reprint requests to Dr. M. M. Verbeek at Department of Pathology, University Hospital Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
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    • 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.

  • Robert M. W. De Waal,

    1. Department of Pathology, University Hospital Nijmegen, Nijmegen, The Netherlands;
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  • Janine J. Schipper,

    1. Department of Microbiology and Molecular Genetics, University of California, Irvine, California; and
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  • William E. Van Nostrand

    1. Department of Microbiology and Molecular Genetics, University of California, Irvine, California; and
    2. Department of Medicine, Health Science Center, State University of New York, Stony Brook, New York, U.S.A.
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Address correspondence and reprint requests to Dr. M. M. Verbeek at Department of Pathology, University Hospital Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.

Abstract

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.

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