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

Bibliographic Details
Main Author: Llorens, Franc
Publication Date: 2020
Other Authors: Hermann, Peter, Villar-Piqué, Anna, Diaz-Lucena, Daniela, Nägga, Katarina, Hansson, Oskar, Santana, Isabel, Schmitz, Matthias, Schmidt, Christian, Varges, Daniela, Goebel, Stefan, Dumurgier, Julien, Zetterberg, Henrik, Blennow, Kaj, Paquet, Claire, Baldeiras, Inês, Ferrer, Isidro, Zerr, Inga
Format: Article
Language: eng
Source: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
Download full: https://hdl.handle.net/10316/106505
https://doi.org/10.1038/s41467-020-14373-2
Summary: 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.
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spelling Cerebrospinal fluid lipocalin 2 as a novel biomarker for the differential diagnosis of vascular dementiaAgedAged, 80 and overAlzheimer DiseaseBiomarkersCerebrovascular DisordersDementia, VascularDiagnosis, DifferentialFemaleHumansLipocalin-2MaleMiddle AgedThe 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.This study was funded by the ADDF (Alzheimer’s Drug Discovery Foundation—Grant 201810- 2017419) to F.L. and I.Z., the Instituto Carlos III (grants CP16/00041 and PI19/00144) to F.L., the Robert Koch Institute through funds from the German Federal Ministry of Health (grant no. 1369–341) to I.Z., and the Spanish Ministry of Health, Instituto Carlos III (Fondo de Investigación Sanitaria—FIS PI14/00757) to I.F. H.Z. is a Wallenberg Academy Fellow supported by grants from the Swedish Research Council, the European Research Council, Swedish State Support for Clinical Research (ALFGBG), and the UK Dementia Research Institute at UCL. K.B. holds the Torsten Söderberg Professorship of Medicine and is supported by grants from the Swedish Research Council, the Swedish Brain Foundation, the Swedish Alzheimer Foundation, and Swedish State Support for Clinical Research (ALFGBG).Springer Nature2020-01-30info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttps://hdl.handle.net/10316/106505https://hdl.handle.net/10316/106505https://doi.org/10.1038/s41467-020-14373-2eng2041-1723Llorens, FrancHermann, PeterVillar-Piqué, AnnaDiaz-Lucena, DanielaNägga, KatarinaHansson, OskarSantana, IsabelSchmitz, MatthiasSchmidt, ChristianVarges, DanielaGoebel, StefanDumurgier, JulienZetterberg, HenrikBlennow, KajPaquet, ClaireBaldeiras, InêsFerrer, IsidroZerr, Ingainfo:eu-repo/semantics/openAccessreponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiainstacron:RCAAP2023-04-06T10:19:57Zoai:estudogeral.uc.pt:10316/106505Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireinfo@rcaap.ptopendoar:https://opendoar.ac.uk/repository/71602025-05-29T05:57:15.242849Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiafalse
dc.title.none.fl_str_mv Cerebrospinal fluid lipocalin 2 as a novel biomarker for the differential diagnosis of vascular dementia
title Cerebrospinal fluid lipocalin 2 as a novel biomarker for the differential diagnosis of vascular dementia
spellingShingle Cerebrospinal fluid lipocalin 2 as a novel biomarker for the differential diagnosis of vascular dementia
Llorens, Franc
Aged
Aged, 80 and over
Alzheimer Disease
Biomarkers
Cerebrovascular Disorders
Dementia, Vascular
Diagnosis, Differential
Female
Humans
Lipocalin-2
Male
Middle Aged
title_short Cerebrospinal fluid lipocalin 2 as a novel biomarker for the differential diagnosis of vascular dementia
title_full Cerebrospinal fluid lipocalin 2 as a novel biomarker for the differential diagnosis of vascular dementia
title_fullStr Cerebrospinal fluid lipocalin 2 as a novel biomarker for the differential diagnosis of vascular dementia
title_full_unstemmed Cerebrospinal fluid lipocalin 2 as a novel biomarker for the differential diagnosis of vascular dementia
title_sort Cerebrospinal fluid lipocalin 2 as a novel biomarker for the differential diagnosis of vascular dementia
author Llorens, Franc
author_facet Llorens, Franc
Hermann, Peter
Villar-Piqué, Anna
Diaz-Lucena, Daniela
Nägga, Katarina
Hansson, Oskar
Santana, Isabel
Schmitz, Matthias
Schmidt, Christian
Varges, Daniela
Goebel, Stefan
Dumurgier, Julien
Zetterberg, Henrik
Blennow, Kaj
Paquet, Claire
Baldeiras, Inês
Ferrer, Isidro
Zerr, Inga
author_role author
author2 Hermann, Peter
Villar-Piqué, Anna
Diaz-Lucena, Daniela
Nägga, Katarina
Hansson, Oskar
Santana, Isabel
Schmitz, Matthias
Schmidt, Christian
Varges, Daniela
Goebel, Stefan
Dumurgier, Julien
Zetterberg, Henrik
Blennow, Kaj
Paquet, Claire
Baldeiras, Inês
Ferrer, Isidro
Zerr, Inga
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Llorens, Franc
Hermann, Peter
Villar-Piqué, Anna
Diaz-Lucena, Daniela
Nägga, Katarina
Hansson, Oskar
Santana, Isabel
Schmitz, Matthias
Schmidt, Christian
Varges, Daniela
Goebel, Stefan
Dumurgier, Julien
Zetterberg, Henrik
Blennow, Kaj
Paquet, Claire
Baldeiras, Inês
Ferrer, Isidro
Zerr, Inga
dc.subject.por.fl_str_mv Aged
Aged, 80 and over
Alzheimer Disease
Biomarkers
Cerebrovascular Disorders
Dementia, Vascular
Diagnosis, Differential
Female
Humans
Lipocalin-2
Male
Middle Aged
topic Aged
Aged, 80 and over
Alzheimer Disease
Biomarkers
Cerebrovascular Disorders
Dementia, Vascular
Diagnosis, Differential
Female
Humans
Lipocalin-2
Male
Middle Aged
description 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.
publishDate 2020
dc.date.none.fl_str_mv 2020-01-30
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv https://hdl.handle.net/10316/106505
https://hdl.handle.net/10316/106505
https://doi.org/10.1038/s41467-020-14373-2
url https://hdl.handle.net/10316/106505
https://doi.org/10.1038/s41467-020-14373-2
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 2041-1723
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Springer Nature
publisher.none.fl_str_mv Springer Nature
dc.source.none.fl_str_mv reponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
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collection Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
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