Non-amyloid cerebral small vessel disease (CSVD) and cerebral amyloid angiopathy (CAA) may be interrelated through the damaged basement membranes (BMs) and extracellular matrix changes of small vessels, resulting in a failure of β-amyloid (Aβ) transport and degradation. We analyzed BM changes and the pattern of deposition of Aβ in the walls of blood vessels in spontaneously hypertensive stroke-prone rats (SHRSP), a non-transgenic CSVD model. In 45 SHRSP and 38 Wistar rats aged 18 to 32 weeks: (i) the percentage area immunostained for vascular collagen IV and laminin was quantified; (ii) the capillary BM thickness as well as endothelial and pericyte pathological changes were analysed using transmission electron microscopy (TEM); and (iii) the presence of vascular Aβ was assessed. Compared with controls, SHRSP exhibited a significantly higher percentage area immunostained with collagen IV in the striatum and thalamus. SHRSP also revealed an age-dependent increase of the capillary BM thickness and of endothelial vacuoles (caveolae) within subcortical regions. Endogenous Aβ deposits in the walls of small blood vessels were observed in the cortex (with the highest incidence found within fronto-parietal areas), striatum, thalamus and hippocampus. Vascular β-amyloid accumulations were frequently detected at sites of small vessel wall damage. Our data demonstrate changes in the expression of collagen IV and of the ultrastructure of BMs in the small vessels of SHRSP. Alterations are accompanied by vascular deposits of endogenous Aβ. Impaired β-amyloid clearance along perivascular and endothelial pathways and failure of extracellular Aβ degradation may be the key mechanisms connecting non-amyloid CSVD and CAA.
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May 2017
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Cover Image
Image demonstrates the ultrastructural cortical basement membrane changes in SHRSP brain: accumulation of lipofuscin in pericytes. For further details, see article by Screiber et al in this issue (pages 1001–1013). Image kindly provided by Stefanie Schreiber.
Research Article|
May 09 2017
Vascular basement membrane alterations and β-amyloid accumulations in an animal model of cerebral small vessel disease
Friederike Held;
Friederike Held
*
1Department of Neurology, Otto-von-Guericke University Magdeburg, Germany, German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany
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Alan W.J. Morris;
Alan W.J. Morris
*
2Faculty of Medicine, University of Southampton, U.K.
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Daniel Pirici;
Daniel Pirici
3Department of Research Methodology, University of Medicine and Pharmacy of Craiova, Romania
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Solveig Niklass;
Solveig Niklass
1Department of Neurology, Otto-von-Guericke University Magdeburg, Germany, German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany
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Matthew M.G. Sharp;
Matthew M.G. Sharp
2Faculty of Medicine, University of Southampton, U.K.
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Cornelia Garz;
Cornelia Garz
1Department of Neurology, Otto-von-Guericke University Magdeburg, Germany, German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany
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Anne Assmann;
Anne Assmann
1Department of Neurology, Otto-von-Guericke University Magdeburg, Germany, German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany
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Hans-Jochen Heinze;
Hans-Jochen Heinze
1Department of Neurology, Otto-von-Guericke University Magdeburg, Germany, German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany
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Frank Schreiber;
Frank Schreiber
1Department of Neurology, Otto-von-Guericke University Magdeburg, Germany, German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany
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Roxana Octavia Carare;
Roxana Octavia Carare
*
2Faculty of Medicine, University of Southampton, U.K.
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Stefanie Schreiber
Stefanie Schreiber
*
1Department of Neurology, Otto-von-Guericke University Magdeburg, Germany, German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany
Correspondence: Stefanie Schreiber ([email protected])
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Publisher: Portland Press Ltd
Received:
January 03 2017
Revision Received:
March 24 2017
Accepted:
March 27 2017
Accepted Manuscript online:
March 27 2017
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2017 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society
2017
Clin Sci (Lond) (2017) 131 (10): 1001–1013.
Article history
Received:
January 03 2017
Revision Received:
March 24 2017
Accepted:
March 27 2017
Accepted Manuscript online:
March 27 2017
Citation
Friederike Held, Alan W.J. Morris, Daniel Pirici, Solveig Niklass, Matthew M.G. Sharp, Cornelia Garz, Anne Assmann, Hans-Jochen Heinze, Frank Schreiber, Roxana Octavia Carare, Stefanie Schreiber; Vascular basement membrane alterations and β-amyloid accumulations in an animal model of cerebral small vessel disease. Clin Sci (Lond) 1 May 2017; 131 (10): 1001–1013. doi: https://doi.org/10.1042/CS20170004
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