title: Alterations of matrix metalloproteinases in the healthy elderly with increased risk of prodromal Alzheimer's disease.
abstract: BACKGROUND
  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.
authors.affiliation: Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University; SUS, 205 02 Malmö, Sweden. erik.stomrud@med.lu.se.
authors.forename: Erik
authors.initials: E
authors.lastname: Stomrud
authors.forename: Maria
authors.initials: M
authors.lastname: Björkqvist
authors.forename: Sabina
authors.initials: S
authors.lastname: Janciauskiene
authors.forename: Lennart
authors.initials: L
authors.lastname: Minthon
authors.forename: Oskar
authors.initials: O
authors.lastname: Hansson