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

Journal of Neuropathology and Experimental Neurology

PubMedID: 24918635

Schultz N, Nielsen HM, Minthon L, Wennström M. Involvement of Matrix Metalloproteinase-9 in Amyloid-ß 1-42-Induced Shedding of the Pericyte Proteoglycan NG2. J Neuropathol Exp Neurol. 2014;73(7):684-92.
Deposition of amyloid-ß (Aß) 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 Aß1-42 effects on microvascular alterations, we investigated whether different aggregation forms of Aß1-42 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 Aß1-42. Conversely, oligomer-enriched preparations of Aß1-42 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 Aß1-42 exposure. Our results, demonstrating an Aß1-42 aggregation-dependent effect on levels of NG2 and MMP-9, support previous studies showing an impact of Aß1-42 on vascular integrity and thereby add to our understanding of mechanisms behind the microvascular changes commonly found in patients with Alzheimer disease.This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.