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; Inga Zerr

doi:10.1038/s41467-020-14373-2

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

Nat Commun. 2020 Jan 30;11(1):619. doi: 10.1038/s41467-020-14373-2.

Authors

Franc Llorens^#^{1

2

3}, Peter Hermann^#⁴, Anna Villar-Piqué^#⁵, Daniela Diaz-Lucena⁶, Katarina Nägga⁷, Oskar Hansson^{8

9}, Isabel Santana¹⁰, Matthias Schmitz^{5

11}, Christian Schmidt^{5

12}, Daniela Varges⁵, Stefan Goebel⁵, Julien Dumurgier¹³, Henrik Zetterberg^{14

15

16

17}, Kaj Blennow^{16

17}, Claire Paquet¹³, Inês Baldeiras¹⁰, Isidro Ferrer^{6

18

19

20}, Inga Zerr^{5

11}

Affiliations

¹ Department of Neurology, University Medical Center Göttingen, Göttingen, Germany. [email protected].
² Network center for biomedical research of neurodegenerative diseases (CIBERNED), Institute Carlos III, Ministry of Health, Llobregat, Spain. [email protected].
³ Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Llobregat, Spain. [email protected].
⁴ Department of Neurology, University Medical Center Göttingen, Göttingen, Germany. [email protected].
⁵ Department of Neurology, University Medical Center Göttingen, Göttingen, Germany.
⁶ Network center for biomedical research of neurodegenerative diseases (CIBERNED), Institute Carlos III, Ministry of Health, Llobregat, Spain.
⁷ Department of Acute Internal Medicine and Geriatrics, Linköping University, Linköping, Sweden.
⁸ Memory Clinic, Skåne University Hospital, Malmö, Sweden.
⁹ Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Malmö, Sweden.
¹⁰ Neurology Department, CHUC-Centro Hospitalar e Universitário de Coimbra, CNC- Center for Neuroscience and Cell Biology; Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
¹¹ German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.
¹² Department of Neurology, Center for Head- and Neuro-Medicine, Klinikum Kassel, Kassel, Germany.
¹³ Center of Cognitive Neurology and Inserm U942 Lariboisière Hospital AP-HP University Paris Diderot, 75010, Paris, France.
¹⁴ Department of Neurodegenerative Disease, Institute of Neurology, University College London, London, UK.
¹⁵ UK Dementia Research Institute at UCL, London, UK.
¹⁶ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
¹⁷ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
¹⁸ Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Llobregat, Spain.
¹⁹ Department of Pathology and Experimental Therapeutics, University of Barcelona, Hospitalet de Llobregat, Spain.
²⁰ Institute of Neurosciences, University of Barcelona, Barcelona, Spain.

^# Contributed equally.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aged, 80 and over
Alzheimer Disease / cerebrospinal fluid*
Alzheimer Disease / diagnosis
Biomarkers / cerebrospinal fluid*
Cerebrovascular Disorders / diagnosis*
Dementia, Vascular / diagnosis*
Diagnosis, Differential
Female
Humans
Lipocalin-2 / cerebrospinal fluid*
Male
Middle Aged

Substances

Biomarkers
LCN2 protein, human
Lipocalin-2