Plasma Lipocalin 2 in Alzheimer's disease: potential utility in the differential diagnosis and relationship with other biomarkers
Autor(a) principal: | |
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Data de Publicação: | 2022 |
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/10316/102836 https://doi.org/10.1186/s13195-021-00955-9 |
Resumo: | Background: Lipocalin-2 is a glycoprotein that is involved in various physiological and pathophysiological processes. In the brain, it is expressed in response to vascular and other brain injury, as well as in Alzheimer’s disease in reactive microglia and astrocytes. Plasma Lipocalin-2 has been proposed as a biomarker for Alzheimer’s disease but available data is scarce and inconsistent. Thus, we evaluated plasma Lipocalin-2 in the context of Alzheimer’s disease, differential diagnoses, other biomarkers, and clinical data. Methods: For this two-center case-control study, we analyzed Lipocalin-2 concentrations in plasma samples from a cohort of n = 407 individuals. The diagnostic groups comprised Alzheimer’s disease (n = 74), vascular dementia (n = 28), other important differential diagnoses (n = 221), and healthy controls (n = 84). Main results were validated in an independent cohort with patients with Alzheimer’s disease (n = 19), mild cognitive impairment (n = 27), and healthy individuals (n = 28). Results: Plasma Lipocalin-2 was significantly lower in Alzheimer’s disease compared to healthy controls (p < 0.001) and all other groups (p < 0.01) except for mixed dementia (vascular and Alzheimer’s pathologic changes). Areas under the curve from receiver operation characteristics for the discrimination of Alzheimer’s disease and healthy controls were 0.783 (95%CI: 0.712–0.855) in the study cohort and 0.766 (95%CI: 0.627–0.905) in the validation cohort. The area under the curve for Alzheimer’s disease versus vascular dementia was 0.778 (95%CI: 0.667–0.890) in the study cohort. In Alzheimer’s disease patients, plasma Lipocalin2 did not show significant correlation with cerebrospinal fluid biomarkers of neurodegeneration and AD-related pathology (total-tau, phosphorylated tau protein, and beta-amyloid 1-42), cognitive status (Mini Mental Status Examination scores), APOE genotype, or presence of white matter hyperintensities. Interestingly, Lipocalin 2 was lower in patients with rapid disease course compared to patients with nonrapidly progressive Alzheimer’s disease (p = 0.013). Conclusions: Plasma Lipocalin-2 has potential as a diagnostic biomarker for Alzheimer’s disease and seems to be independent from currently employed biomarkers. |
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Plasma Lipocalin 2 in Alzheimer's disease: potential utility in the differential diagnosis and relationship with other biomarkersDementiaAlzheimer’s diseaseBiomarkerPlasmaLipocalin 2Neutrophil gelatinase-associated LipocalinAmyloid beta-PeptidesCase-Control StudiesCognitive DysfunctionDiagnosis, DifferentialHumansLipocalin-2tau ProteinsAlzheimer DiseaseBiomarkersBackground: Lipocalin-2 is a glycoprotein that is involved in various physiological and pathophysiological processes. In the brain, it is expressed in response to vascular and other brain injury, as well as in Alzheimer’s disease in reactive microglia and astrocytes. Plasma Lipocalin-2 has been proposed as a biomarker for Alzheimer’s disease but available data is scarce and inconsistent. Thus, we evaluated plasma Lipocalin-2 in the context of Alzheimer’s disease, differential diagnoses, other biomarkers, and clinical data. Methods: For this two-center case-control study, we analyzed Lipocalin-2 concentrations in plasma samples from a cohort of n = 407 individuals. The diagnostic groups comprised Alzheimer’s disease (n = 74), vascular dementia (n = 28), other important differential diagnoses (n = 221), and healthy controls (n = 84). Main results were validated in an independent cohort with patients with Alzheimer’s disease (n = 19), mild cognitive impairment (n = 27), and healthy individuals (n = 28). Results: Plasma Lipocalin-2 was significantly lower in Alzheimer’s disease compared to healthy controls (p < 0.001) and all other groups (p < 0.01) except for mixed dementia (vascular and Alzheimer’s pathologic changes). Areas under the curve from receiver operation characteristics for the discrimination of Alzheimer’s disease and healthy controls were 0.783 (95%CI: 0.712–0.855) in the study cohort and 0.766 (95%CI: 0.627–0.905) in the validation cohort. The area under the curve for Alzheimer’s disease versus vascular dementia was 0.778 (95%CI: 0.667–0.890) in the study cohort. In Alzheimer’s disease patients, plasma Lipocalin2 did not show significant correlation with cerebrospinal fluid biomarkers of neurodegeneration and AD-related pathology (total-tau, phosphorylated tau protein, and beta-amyloid 1-42), cognitive status (Mini Mental Status Examination scores), APOE genotype, or presence of white matter hyperintensities. Interestingly, Lipocalin 2 was lower in patients with rapid disease course compared to patients with nonrapidly progressive Alzheimer’s disease (p = 0.013). Conclusions: Plasma Lipocalin-2 has potential as a diagnostic biomarker for Alzheimer’s disease and seems to be independent from currently employed biomarkers.Open Access funding enabled and organized by Projekt DEAL. This study was funded by the ADDF (Alzheimer’s Drug Discovery Foundation: Grant 201810-2017419) to FL and IZ, the Instituto Carlos III (grants CP16/00041 and PI19/00144) to FL, the Robert Koch Institute through funds from the German Federal Ministry of Health (grant no. 1369–341) to IZ, and the Alzheimer Forschung Initiative (AFI, project no. 20026) to MS2022info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/102836http://hdl.handle.net/10316/102836https://doi.org/10.1186/s13195-021-00955-9eng1758-9193Hermann, PeterVillar-Piqué, AnnaSchmitz, MatthiasSchmidt, ChristianVarges, DanielaGoebel, StefanBunck, TimothyLindemann, HannaBogner, CarlaSantana, IsabelBaldeiras, InêsRiggert, JoachimZerr, IngaLlorens, Francinfo: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:RCAAP2023-04-06T10:20:22Zoai:estudogeral.uc.pt:10316/102836Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:19:44.949010Repositório 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 |
Plasma Lipocalin 2 in Alzheimer's disease: potential utility in the differential diagnosis and relationship with other biomarkers |
title |
Plasma Lipocalin 2 in Alzheimer's disease: potential utility in the differential diagnosis and relationship with other biomarkers |
spellingShingle |
Plasma Lipocalin 2 in Alzheimer's disease: potential utility in the differential diagnosis and relationship with other biomarkers Hermann, Peter Dementia Alzheimer’s disease Biomarker Plasma Lipocalin 2 Neutrophil gelatinase-associated Lipocalin Amyloid beta-Peptides Case-Control Studies Cognitive Dysfunction Diagnosis, Differential Humans Lipocalin-2 tau Proteins Alzheimer Disease Biomarkers |
title_short |
Plasma Lipocalin 2 in Alzheimer's disease: potential utility in the differential diagnosis and relationship with other biomarkers |
title_full |
Plasma Lipocalin 2 in Alzheimer's disease: potential utility in the differential diagnosis and relationship with other biomarkers |
title_fullStr |
Plasma Lipocalin 2 in Alzheimer's disease: potential utility in the differential diagnosis and relationship with other biomarkers |
title_full_unstemmed |
Plasma Lipocalin 2 in Alzheimer's disease: potential utility in the differential diagnosis and relationship with other biomarkers |
title_sort |
Plasma Lipocalin 2 in Alzheimer's disease: potential utility in the differential diagnosis and relationship with other biomarkers |
author |
Hermann, Peter |
author_facet |
Hermann, Peter Villar-Piqué, Anna Schmitz, Matthias Schmidt, Christian Varges, Daniela Goebel, Stefan Bunck, Timothy Lindemann, Hanna Bogner, Carla Santana, Isabel Baldeiras, Inês Riggert, Joachim Zerr, Inga Llorens, Franc |
author_role |
author |
author2 |
Villar-Piqué, Anna Schmitz, Matthias Schmidt, Christian Varges, Daniela Goebel, Stefan Bunck, Timothy Lindemann, Hanna Bogner, Carla Santana, Isabel Baldeiras, Inês Riggert, Joachim Zerr, Inga Llorens, Franc |
author2_role |
author author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Hermann, Peter Villar-Piqué, Anna Schmitz, Matthias Schmidt, Christian Varges, Daniela Goebel, Stefan Bunck, Timothy Lindemann, Hanna Bogner, Carla Santana, Isabel Baldeiras, Inês Riggert, Joachim Zerr, Inga Llorens, Franc |
dc.subject.por.fl_str_mv |
Dementia Alzheimer’s disease Biomarker Plasma Lipocalin 2 Neutrophil gelatinase-associated Lipocalin Amyloid beta-Peptides Case-Control Studies Cognitive Dysfunction Diagnosis, Differential Humans Lipocalin-2 tau Proteins Alzheimer Disease Biomarkers |
topic |
Dementia Alzheimer’s disease Biomarker Plasma Lipocalin 2 Neutrophil gelatinase-associated Lipocalin Amyloid beta-Peptides Case-Control Studies Cognitive Dysfunction Diagnosis, Differential Humans Lipocalin-2 tau Proteins Alzheimer Disease Biomarkers |
description |
Background: Lipocalin-2 is a glycoprotein that is involved in various physiological and pathophysiological processes. In the brain, it is expressed in response to vascular and other brain injury, as well as in Alzheimer’s disease in reactive microglia and astrocytes. Plasma Lipocalin-2 has been proposed as a biomarker for Alzheimer’s disease but available data is scarce and inconsistent. Thus, we evaluated plasma Lipocalin-2 in the context of Alzheimer’s disease, differential diagnoses, other biomarkers, and clinical data. Methods: For this two-center case-control study, we analyzed Lipocalin-2 concentrations in plasma samples from a cohort of n = 407 individuals. The diagnostic groups comprised Alzheimer’s disease (n = 74), vascular dementia (n = 28), other important differential diagnoses (n = 221), and healthy controls (n = 84). Main results were validated in an independent cohort with patients with Alzheimer’s disease (n = 19), mild cognitive impairment (n = 27), and healthy individuals (n = 28). Results: Plasma Lipocalin-2 was significantly lower in Alzheimer’s disease compared to healthy controls (p < 0.001) and all other groups (p < 0.01) except for mixed dementia (vascular and Alzheimer’s pathologic changes). Areas under the curve from receiver operation characteristics for the discrimination of Alzheimer’s disease and healthy controls were 0.783 (95%CI: 0.712–0.855) in the study cohort and 0.766 (95%CI: 0.627–0.905) in the validation cohort. The area under the curve for Alzheimer’s disease versus vascular dementia was 0.778 (95%CI: 0.667–0.890) in the study cohort. In Alzheimer’s disease patients, plasma Lipocalin2 did not show significant correlation with cerebrospinal fluid biomarkers of neurodegeneration and AD-related pathology (total-tau, phosphorylated tau protein, and beta-amyloid 1-42), cognitive status (Mini Mental Status Examination scores), APOE genotype, or presence of white matter hyperintensities. Interestingly, Lipocalin 2 was lower in patients with rapid disease course compared to patients with nonrapidly progressive Alzheimer’s disease (p = 0.013). Conclusions: Plasma Lipocalin-2 has potential as a diagnostic biomarker for Alzheimer’s disease and seems to be independent from currently employed biomarkers. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022 |
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/10316/102836 http://hdl.handle.net/10316/102836 https://doi.org/10.1186/s13195-021-00955-9 |
url |
http://hdl.handle.net/10316/102836 https://doi.org/10.1186/s13195-021-00955-9 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1758-9193 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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