title: Cerebrovascular Biomarker Profile Is Related to White Matter Disease and Ventricular Dilation in a LADIS Substudy.
abstract: BACKGROUND
  Small vessel disease (SVD) represents a common often progressive condition in elderly people contributing to cognitive disability. The relationship between cerebrospinal fluid (CSF) biomarkers and imaging correlates of SVD was investigated, and the findings were hypothesized to be associated with a neuropsychological profile of SVD.
  
  
  METHODS
  CSF SVD-related biomarkers [neurofilament light (NF-L), myelin basic protein (MBP), soluble amyloid precursor protein-β (sAPPβ), matrix metalloproteinases (MMPs), and tissue inhibitor of metalloproteinase (TIMP)] were analysed in 46 non-demented elderly with imaging findings of SVD. We assessed the relationship between the CSF biomarkers and white matter hyperintensity (WMH) volume, diffusion-weighted imaging and atrophy as well as their association with neuropsychological profiles.
  
  
  RESULTS
  The WMH volume correlated with ventricular dilation, which was associated with executive function and speed and attention. Increased WMH and ventricular dilation were related to increased CSF levels of TIMP-1, NF-L and MBP and to decreased sAPPβ. A positive correlation was found between the CSF biomarker MMP-9 and WMH progression.
  
  
  CONCLUSIONS
  The link between progressive WMH and MMP-9 suggests an involvement of the enzyme in white matter degeneration. CSF TIMP-1, NF-L, MBP and sAPPβ may function as biological markers of white matter damage.
authors.affiliation: Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Bjerke
authors.affiliation: Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
authors.forename: Michael
authors.initials: M
authors.lastname: Jonsson
authors.affiliation: Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
authors.forename: Arto
authors.initials: A
authors.lastname: Nordlund
authors.affiliation: Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
authors.forename: Carl
authors.initials: C
authors.lastname: Eckerström
authors.affiliation: Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.affiliation: Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden ; UCL Institute of Neurology, London, UK.
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.affiliation: Department of Neurological and Psychiatric Sciences, University of Florence, Florence, Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Pantoni
authors.affiliation: Department of Neurological and Psychiatric Sciences, University of Florence, Florence, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Inzitari
authors.affiliation: Department of Clinical Neurogeriatrics, Medical University of Graz, Graz, Austria.
authors.forename: Reinhold
authors.initials: R
authors.lastname: Schmidt
authors.affiliation: Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Wallin
keywords: Biomarkers; Cerebrospinal fluid; Matrix metalloproteinases; Myelin basic protein; Neurofilament; Ventricular dilation; White matter disease