title: Early changes in extracellular matrix in Alzheimer's disease.
abstract: OBJECTIVE
  Although changes in extracellular matrix (ECM) scaffold have been reported previously in Alzheimer's disease (AD) compared to normal ageing, it is not known how alterations in the numerous components of the perivascular ECM might occur at different stages of AD. This study therefore investigates potential changes in basement membrane-associated ECM molecules in relation to increasing Braak stages.
  
  
  METHODS
  Thirty patients were divided into three groups (control subject, subclinical AD and AD patients). ECM levels of collagen IV, perlecan and fibronectin as well as human platelet endothelial cell adhesion molecule (hPECAM) were quantified by immunohistochemistry. Von Willebrand factor staining was measured to assess vessel density. Expression levels were correlated with the presence of amyloid plaques.
  
  
  RESULTS
  Collagen IV, perlecan and fibronectin expression was increased in subclinical AD and AD patients when compared to controls, in frontal and temporal cortex, whilst no further increase was detected between subclinical AD and AD. These changes were not associated with an increase in vessel density, which was instead decreased in the temporal cortex of AD patients. In contrast, hPECAM levels remained unchanged. Finally, we found similar pattern in levels of amyloid deposition between the different Braak stages and showed that changes in ECM components correlated with amyloid deposition.
  
  
  CONCLUSIONS
  Present data support the hypothesis that significant ECM changes occur during the early stages of AD. ECM changes affecting brain microvascular functions could therefore drive disease progression and provide potential new early investigational biomarkers in AD.
authors.affiliation: Wolfson Molecular Imaging Centre, University of Manchester, Manchester, UK.|Faculty of Medical and Human Sciences, Institute of Brain, Behaviour and Mental Health, University of Manchester, Manchester, UK.
authors.forename: F-X
authors.initials: FX
authors.lastname: Lepelletier
authors.affiliation: Faculty of Medical and Human Sciences, Institute of Brain, Behaviour and Mental Health, University of Manchester, Manchester, UK.|Department of Clinical and Cognitive Neurosciences, Salford Royal NHS Foundation Trust, Salford, UK.
authors.forename: D M A
authors.initials: DM
authors.lastname: Mann
authors.affiliation: Faculty of Medical and Human Sciences, Institute of Brain, Behaviour and Mental Health, University of Manchester, Manchester, UK.|Department of Clinical and Cognitive Neurosciences, Salford Royal NHS Foundation Trust, Salford, UK.
authors.forename: A C
authors.initials: AC
authors.lastname: Robinson
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester, UK.
authors.forename: E
authors.initials: E
authors.lastname: Pinteaux
authors.affiliation: Wolfson Molecular Imaging Centre, University of Manchester, Manchester, UK.|Faculty of Medical and Human Sciences, Institute of Population Health, University of Manchester, Manchester, UK.
authors.forename: H
authors.initials: H
authors.lastname: Boutin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D005109:Extracellular Matrix / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged
keywords: Alzheimer's disease; basement membrane; collagen IV; fibronectin; human platelet endothelial cell adhesion molecule; perlecan