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Alterations of matrix metalloproteinases in the healthy elderly with increased risk of prodromal Alzheimer's disease

Stomrud, Erik LU orcid ; Björkqvist, Maria LU orcid ; Janciauskiene, Sabina LU ; Minthon, Lennart LU and Hansson, Oskar LU orcid (2010) In Alzheimer's Research & Therapy 2(3). p.20-20
Abstract

INTRODUCTION: Matrix metalloproteinases (MMP) are believed to be involved in the pathologic processes behind Alzheimer's disease (AD). In this study, we aimed to examine the cerebrospinal fluid (CSF) levels of MMPs and tissue inhibitors of metalloproteinase-1 (TIMP-1) in individuals with AD dementia and cognitively healthy elderly individuals, and to investigate their relationship with established CSF biomarkers for Alzheimer's disease.

METHODS: CSF was collected from 38 individuals with AD dementia and 34 cognitively healthy elderly individuals. The CSF was analyzed for MMP-1, MMP-3, MMP-9, TIMP-1, beta-amyloid1-42 (Abeta42), total tau protein (T-tau) and phosphorylated tau protein (P-tau). MMP/TIMP-1 ratios were calculated. APOE... (More)

INTRODUCTION: Matrix metalloproteinases (MMP) are believed to be involved in the pathologic processes behind Alzheimer's disease (AD). In this study, we aimed to examine the cerebrospinal fluid (CSF) levels of MMPs and tissue inhibitors of metalloproteinase-1 (TIMP-1) in individuals with AD dementia and cognitively healthy elderly individuals, and to investigate their relationship with established CSF biomarkers for Alzheimer's disease.

METHODS: CSF was collected from 38 individuals with AD dementia and 34 cognitively healthy elderly individuals. The CSF was analyzed for MMP-1, MMP-3, MMP-9, TIMP-1, beta-amyloid1-42 (Abeta42), total tau protein (T-tau) and phosphorylated tau protein (P-tau). MMP/TIMP-1 ratios were calculated. APOE genotype was determined for the participants.

RESULTS: AD patients had higher MMP-9/TIMP-1 ratios and lower TIMP-1 levels compared to cognitively healthy individuals. In AD patients, the MMP-9/TIMP-1 ratio correlated with CSF T-tau, a marker of neurodegeneration. Interestingly, the cognitively healthy individuals with risk markers for future AD, i.e. AD-supportive CSF biomarker levels of T-tau, P-tau and Abeta42 or the presence of the APOE epsilon4 allele, had higher CSF MMP-3 and MMP-9 levels and higher CSF MMP-3/TIMP-1 ratios compared to the healthy individuals without risk markers. The CSF levels of MMP-3 and -9 in the control group also correlated with the CSF T-tau and P-tau levels.

CONCLUSIONS: This study indicates that MMP-3 and MMP-9 might be involved in early pathogenesis of AD and that MMPs could be associated with neuronal degeneration and formation of neurofibrillary tangles even prior to development of overt cognitive dysfunction.

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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Alzheimer's Research & Therapy
volume
2
issue
3
pages
20 - 20
publisher
BioMed Central (BMC)
external identifiers
  • pmid:20576109
  • scopus:77954788631
ISSN
1758-9193
DOI
10.1186/alzrt44
language
English
LU publication?
yes
id
c0429340-17dd-4fbc-9414-de7c5c5b7936
date added to LUP
2019-05-31 13:14:49
date last changed
2024-06-26 19:30:22
@article{c0429340-17dd-4fbc-9414-de7c5c5b7936,
  abstract     = {{<p>INTRODUCTION: Matrix metalloproteinases (MMP) are believed to be involved in the pathologic processes behind Alzheimer's disease (AD). In this study, we aimed to examine the cerebrospinal fluid (CSF) levels of MMPs and tissue inhibitors of metalloproteinase-1 (TIMP-1) in individuals with AD dementia and cognitively healthy elderly individuals, and to investigate their relationship with established CSF biomarkers for Alzheimer's disease.</p><p>METHODS: CSF was collected from 38 individuals with AD dementia and 34 cognitively healthy elderly individuals. The CSF was analyzed for MMP-1, MMP-3, MMP-9, TIMP-1, beta-amyloid1-42 (Abeta42), total tau protein (T-tau) and phosphorylated tau protein (P-tau). MMP/TIMP-1 ratios were calculated. APOE genotype was determined for the participants.</p><p>RESULTS: AD patients had higher MMP-9/TIMP-1 ratios and lower TIMP-1 levels compared to cognitively healthy individuals. In AD patients, the MMP-9/TIMP-1 ratio correlated with CSF T-tau, a marker of neurodegeneration. Interestingly, the cognitively healthy individuals with risk markers for future AD, i.e. AD-supportive CSF biomarker levels of T-tau, P-tau and Abeta42 or the presence of the APOE epsilon4 allele, had higher CSF MMP-3 and MMP-9 levels and higher CSF MMP-3/TIMP-1 ratios compared to the healthy individuals without risk markers. The CSF levels of MMP-3 and -9 in the control group also correlated with the CSF T-tau and P-tau levels.</p><p>CONCLUSIONS: This study indicates that MMP-3 and MMP-9 might be involved in early pathogenesis of AD and that MMPs could be associated with neuronal degeneration and formation of neurofibrillary tangles even prior to development of overt cognitive dysfunction.</p>}},
  author       = {{Stomrud, Erik and Björkqvist, Maria and Janciauskiene, Sabina and Minthon, Lennart and Hansson, Oskar}},
  issn         = {{1758-9193}},
  language     = {{eng}},
  month        = {{06}},
  number       = {{3}},
  pages        = {{20--20}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{Alzheimer's Research & Therapy}},
  title        = {{Alterations of matrix metalloproteinases in the healthy elderly with increased risk of prodromal Alzheimer's disease}},
  url          = {{http://dx.doi.org/10.1186/alzrt44}},
  doi          = {{10.1186/alzrt44}},
  volume       = {{2}},
  year         = {{2010}},
}