Cerebrospinal fluid lipocalin 2 as a novel biomarker for the differential diagnosis of vascular dementia
Autor(a) principal: | |
---|---|
Data de Publicação: | 2020 |
Outros Autores: | , , , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10316/106505 https://doi.org/10.1038/s41467-020-14373-2 |
Resumo: | 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. |
id |
RCAP_1e214f3edfb983c15080b6fbb8fa3a78 |
---|---|
oai_identifier_str |
oai:estudogeral.uc.pt:10316/106505 |
network_acronym_str |
RCAP |
network_name_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository_id_str |
7160 |
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/articlehttp://hdl.handle.net/10316/106505http://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:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-04-06T10:19:57Zoai:estudogeral.uc.pt:10316/106505Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:22:57.157051Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
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 |
http://hdl.handle.net/10316/106505 http://hdl.handle.net/10316/106505 https://doi.org/10.1038/s41467-020-14373-2 |
url |
http://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:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
|
_version_ |
1799134117349031936 |