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Involvement of Matrix Metalloproteinase-9 in Amyloid-β 1-42-Induced Shedding of the Pericyte Proteoglycan NG2.

Schultz, Nina LU ; Nielsen, Henrietta LU ; Minthon, Lennart LU and Wennström, Malin LU (2014) In Journal of Neuropathology and Experimental Neurology 73(7). p.684-692
Abstract
Deposition of amyloid-β (Aβ) 1-42, the major component of senile plaques characteristic of Alzheimer disease, affects brain microvascular integrity and causes blood-brain barrier dysfunction, increased angiogenesis, and pericyte degeneration. To understand the cellular events underlying Aβ1-42 effects on microvascular alterations, we investigated whether different aggregation forms of Aβ1-42 affect shedding of the pericyte proteoglycan NG2 and whether they affect proteolytic cleavage mediated by matrix metalloproteinase (MMP)-9. We found decreased levels of soluble NG2, total MMP-9, and MMP-9 activity in pericyte culture supernatants in response to fibril-enriched preparations of Aβ1-42. Conversely, oligomer-enriched preparations of Aβ1-42... (More)
Deposition of amyloid-β (Aβ) 1-42, the major component of senile plaques characteristic of Alzheimer disease, affects brain microvascular integrity and causes blood-brain barrier dysfunction, increased angiogenesis, and pericyte degeneration. To understand the cellular events underlying Aβ1-42 effects on microvascular alterations, we investigated whether different aggregation forms of Aβ1-42 affect shedding of the pericyte proteoglycan NG2 and whether they affect proteolytic cleavage mediated by matrix metalloproteinase (MMP)-9. We found decreased levels of soluble NG2, total MMP-9, and MMP-9 activity in pericyte culture supernatants in response to fibril-enriched preparations of Aβ1-42. Conversely, oligomer-enriched preparations of Aβ1-42 increased soluble NG2 levels in the supernatants. This increase was ablated by the MMP-9/MMP-2 inhibitor SB-3CT. There was also a trend toward increased MMP-9 activity observed after oligomeric Aβ1-42 exposure. Our results, demonstrating an Aβ1-42 aggregation-dependent effect on levels of NG2 and MMP-9, support previous studies showing an impact of Aβ1-42 on vascular integrity and thereby add to our understanding of mechanisms behind the microvascular changes commonly found in patients with Alzheimer disease. (Less)
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Contribution to journal
publication status
published
subject
in
Journal of Neuropathology and Experimental Neurology
volume
73
issue
7
pages
684 - 692
publisher
American Association of Neuropathologists
external identifiers
  • pmid:24918635
  • wos:000338133900004
  • scopus:84903314983
ISSN
1554-6578
DOI
10.1097/NEN.0000000000000084
language
English
LU publication?
yes
id
7060b2a1-fc7e-4b63-9663-e46cc983cabb (old id 4528798)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24918635?dopt=Abstract
date added to LUP
2014-07-05 17:17:34
date last changed
2017-11-19 03:02:23
@article{7060b2a1-fc7e-4b63-9663-e46cc983cabb,
  abstract     = {Deposition of amyloid-β (Aβ) 1-42, the major component of senile plaques characteristic of Alzheimer disease, affects brain microvascular integrity and causes blood-brain barrier dysfunction, increased angiogenesis, and pericyte degeneration. To understand the cellular events underlying Aβ1-42 effects on microvascular alterations, we investigated whether different aggregation forms of Aβ1-42 affect shedding of the pericyte proteoglycan NG2 and whether they affect proteolytic cleavage mediated by matrix metalloproteinase (MMP)-9. We found decreased levels of soluble NG2, total MMP-9, and MMP-9 activity in pericyte culture supernatants in response to fibril-enriched preparations of Aβ1-42. Conversely, oligomer-enriched preparations of Aβ1-42 increased soluble NG2 levels in the supernatants. This increase was ablated by the MMP-9/MMP-2 inhibitor SB-3CT. There was also a trend toward increased MMP-9 activity observed after oligomeric Aβ1-42 exposure. Our results, demonstrating an Aβ1-42 aggregation-dependent effect on levels of NG2 and MMP-9, support previous studies showing an impact of Aβ1-42 on vascular integrity and thereby add to our understanding of mechanisms behind the microvascular changes commonly found in patients with Alzheimer disease.},
  author       = {Schultz, Nina and Nielsen, Henrietta and Minthon, Lennart and Wennström, Malin},
  issn         = {1554-6578},
  language     = {eng},
  number       = {7},
  pages        = {684--692},
  publisher    = {American Association of Neuropathologists},
  series       = {Journal of Neuropathology and Experimental Neurology},
  title        = {Involvement of Matrix Metalloproteinase-9 in Amyloid-β 1-42-Induced Shedding of the Pericyte Proteoglycan NG2.},
  url          = {http://dx.doi.org/10.1097/NEN.0000000000000084},
  volume       = {73},
  year         = {2014},
}