Cerebrospinal fluid lipocalin 2 as a novel biomarker for the differential diagnosis of vascular dementia

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The clinical diagnosis of vascular dementia (VaD) is based on imaging criteria, and specific biochemical markers are not available. Here, we investigated the potential of cerebrospinal fluid (CSF) lipocalin 2 (LCN2), a secreted glycoprotein that has been suggested as mediating neuronal damage in vascular brain injuries. The study included four independent cohorts with a total n = 472 samples. LCN2 was significantly elevated in VaD compared to controls, Alzheimer’s disease (AD), other neurodegenerative dementias, and cognitively unimpaired patients with cerebrovascular disease. LCN2 discriminated VaD from AD without coexisting VaD with high accuracy. The main findings were consistent over all cohorts. Neuropathology disclosed a high percentage of macrophages linked to subacute infarcts, reactive astrocytes, and damaged blood vessels in multi-infarct dementia when compared to AD. We conclude that CSF LCN2 is a promising candidate biochemical marker in the differential diagnosis of VaD and neurodegenerative dementias.


  • Franc Llorens
  • Peter Hermann
  • Anna Villar-Piqué
  • Daniela Diaz-Lucena
  • Katarina Nägga
  • Oskar Hansson
  • Isabel Santana
  • Matthias Schmitz
  • Christian Schmidt
  • Daniela Varges
  • Stefan Goebel
  • Julien Dumurgier
  • Henrik Zetterberg
  • Kaj Blennow
  • Claire Paquet
  • Inês Baldeiras
  • Isidro Ferrer
  • Inga Zerr
External organisations
  • University Medical Center Göttingen
  • Carlos III Health Institute
  • Bellvitge University Hospital-IDIBELL
  • Linköping University
  • Skåne University Hospital
  • University of Coimbra
  • German Center for Neurodegenerative Diseases (DZNE), Bonn
  • Lariboisière Hospital
  • University College London
  • Sahlgrenska University Hospital
  • Sahlgrenska Academy
  • University of Barcelona
  • Paris Diderot University
  • University Hospital of Coimbra
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurology
Original languageEnglish
Article number619
JournalNature Communications
Publication statusPublished - 2020 Jan 30
Publication categoryResearch