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Vascular basement membrane alterations and β-amyloid accumulations in an animal model of cerebral small vessel disease

Vascular basement membrane alterations and β-amyloid accumulations in an animal model of cerebral small vessel disease
Vascular basement membrane alterations and β-amyloid accumulations in an animal model of cerebral small vessel disease

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.

Amyloid beta-Peptides, Animals, Basement Membrane, Cerebral Amyloid Angiopathy, Cerebral Small Vessel Diseases, Disease Models, Animal, Humans, Microvessels, Rats, Rats, Inbred SHR, Rats, Wistar, Journal Article
0143-5221
1001-1013
Held, Friederike
d4488dad-310f-4bc3-9d70-aae7eec9716c
Morris, Alan W.J.
e70d7160-c9d9-4035-90b8-9006a1052551
Pirici, Daniel
4a62eb05-a2ae-4594-baa6-8afd720cd939
Niklass, Solveig
583e0ecb-9cf4-47c8-9f97-c39949decd4f
Sharp, Matthew M.G.
ec57c53a-a10a-4b8a-94fe-03eca85ab7c3
Garz, Cornelia
beb2ed6d-1934-4742-8693-2f433c5b9b69
Assmann, Anne
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Heinze, Hans-Jochen
e5b52444-3fcb-4abc-be1c-416bf91d7986
Schreiber, Frank
996cc9b1-c439-4fae-8a46-43b94608d034
Carare, Roxana Octavia
0478c197-b0c1-4206-acae-54e88c8f21fa
Schreiber, Stefanie
0d270570-e83c-46e5-b241-04deeb2d1767
Held, Friederike
d4488dad-310f-4bc3-9d70-aae7eec9716c
Morris, Alan W.J.
e70d7160-c9d9-4035-90b8-9006a1052551
Pirici, Daniel
4a62eb05-a2ae-4594-baa6-8afd720cd939
Niklass, Solveig
583e0ecb-9cf4-47c8-9f97-c39949decd4f
Sharp, Matthew M.G.
ec57c53a-a10a-4b8a-94fe-03eca85ab7c3
Garz, Cornelia
beb2ed6d-1934-4742-8693-2f433c5b9b69
Assmann, Anne
629ff673-3688-4d2a-94b0-e6373903a096
Heinze, Hans-Jochen
e5b52444-3fcb-4abc-be1c-416bf91d7986
Schreiber, Frank
996cc9b1-c439-4fae-8a46-43b94608d034
Carare, Roxana Octavia
0478c197-b0c1-4206-acae-54e88c8f21fa
Schreiber, Stefanie
0d270570-e83c-46e5-b241-04deeb2d1767

Held, Friederike, Morris, Alan W.J., Pirici, Daniel, Niklass, Solveig, Sharp, Matthew M.G., Garz, Cornelia, Assmann, Anne, Heinze, Hans-Jochen, Schreiber, Frank, Carare, Roxana Octavia and Schreiber, Stefanie (2017) Vascular basement membrane alterations and β-amyloid accumulations in an animal model of cerebral small vessel disease. Clinical Science, 131 (10), 1001-1013. (doi:10.1042/CS20170004).

Record type: Article

Abstract

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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More information

e-pub ahead of print date: 9 May 2017
Published date: May 2017
Additional Information: © 2017 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.
Keywords: Amyloid beta-Peptides, Animals, Basement Membrane, Cerebral Amyloid Angiopathy, Cerebral Small Vessel Diseases, Disease Models, Animal, Humans, Microvessels, Rats, Rats, Inbred SHR, Rats, Wistar, Journal Article

Identifiers

Local EPrints ID: 420319
URI: https://eprints.soton.ac.uk/id/eprint/420319
ISSN: 0143-5221
PURE UUID: 807426ba-a5b5-425f-b3bd-d3096440449e
ORCID for Matthew M.G. Sharp: ORCID iD orcid.org/0000-0002-6623-5078

Catalogue record

Date deposited: 04 May 2018 16:30
Last modified: 03 Dec 2019 01:41

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