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

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 and Inga Zerr
Additional contact information
Franc Llorens: University Medical Center Göttingen
Peter Hermann: University Medical Center Göttingen
Anna Villar-Piqué: University Medical Center Göttingen
Daniela Diaz-Lucena: Network center for biomedical research of neurodegenerative diseases (CIBERNED), Institute Carlos III, Ministry of Health
Katarina Nägga: Linköping University
Oskar Hansson: Memory Clinic, Skåne University Hospital
Isabel Santana: University of Coimbra
Matthias Schmitz: University Medical Center Göttingen
Christian Schmidt: University Medical Center Göttingen
Daniela Varges: University Medical Center Göttingen
Stefan Goebel: University Medical Center Göttingen
Julien Dumurgier: Center of Cognitive Neurology and Inserm U942 Lariboisière Hospital AP-HP University Paris Diderot
Henrik Zetterberg: University College London
Kaj Blennow: Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital
Claire Paquet: Center of Cognitive Neurology and Inserm U942 Lariboisière Hospital AP-HP University Paris Diderot
Inês Baldeiras: University of Coimbra
Isidro Ferrer: Network center for biomedical research of neurodegenerative diseases (CIBERNED), Institute Carlos III, Ministry of Health
Inga Zerr: University Medical Center Göttingen

Nature Communications, 2020, vol. 11, issue 1, 1-11

Abstract: Abstract 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.

Date: 2020
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DOI: 10.1038/s41467-020-14373-2

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