Plasma Lipocalin 2 in Alzheimer’s disease: potential utility in the differential diagnosis and relationship with other biomarkers
Abstract 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 b...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-01-01
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| Series: | Alzheimer’s Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13195-021-00955-9 |
| _version_ | 1818753873455611904 |
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| author | Peter Hermann Anna Villar-Piqué Matthias Schmitz Christian Schmidt Daniela Varges Stefan Goebel Timothy Bunck Hanna Lindemann Carla Bogner Isabel Santana Inês Baldeiras Joachim Riggert Inga Zerr Franc Llorens |
| author_facet | Peter Hermann Anna Villar-Piqué Matthias Schmitz Christian Schmidt Daniela Varges Stefan Goebel Timothy Bunck Hanna Lindemann Carla Bogner Isabel Santana Inês Baldeiras Joachim Riggert Inga Zerr Franc Llorens |
| author_sort | Peter Hermann |
| collection | DOAJ |
| description | Abstract 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 non-rapidly 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. |
| first_indexed | 2024-12-18T05:14:16Z |
| format | Article |
| id | doaj.art-bfdd3e3dabd947a9aa2032a068c953f2 |
| institution | Directory Open Access Journal |
| issn | 1758-9193 |
| language | English |
| last_indexed | 2024-12-18T05:14:16Z |
| publishDate | 2022-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Alzheimer’s Research & Therapy |
| spelling | doaj.art-bfdd3e3dabd947a9aa2032a068c953f22022-12-21T21:19:49ZengBMCAlzheimer’s Research & Therapy1758-91932022-01-0114111210.1186/s13195-021-00955-9Plasma Lipocalin 2 in Alzheimer’s disease: potential utility in the differential diagnosis and relationship with other biomarkersPeter Hermann0Anna Villar-Piqué1Matthias Schmitz2Christian Schmidt3Daniela Varges4Stefan Goebel5Timothy Bunck6Hanna Lindemann7Carla Bogner8Isabel Santana9Inês Baldeiras10Joachim Riggert11Inga Zerr12Franc Llorens13Department of Neurology, Clinical Dementia Center and National Reference Center for CJD Surveillance, University Medical Center GöttingenNetwork Center for Biomedical Research in Neurodegenerative Diseases, (CIBERNED), Institute Carlos IIIDepartment of Neurology, Clinical Dementia Center and National Reference Center for CJD Surveillance, University Medical Center GöttingenDepartment of Neurology, Clinical Dementia Center and National Reference Center for CJD Surveillance, University Medical Center GöttingenDepartment of Neurology, Clinical Dementia Center and National Reference Center for CJD Surveillance, University Medical Center GöttingenDepartment of Neurology, Clinical Dementia Center and National Reference Center for CJD Surveillance, University Medical Center GöttingenDepartment of Neurology, Clinical Dementia Center and National Reference Center for CJD Surveillance, University Medical Center GöttingenDepartment of Neurology, Clinical Dementia Center and National Reference Center for CJD Surveillance, University Medical Center GöttingenDepartment of Neurology, Clinical Dementia Center and National Reference Center for CJD Surveillance, University Medical Center GöttingenNeurology Department, CHUC - Centro Hospitalar e Universitário de Coimbra, CNC- Center for Neuroscience and Cell Biology, University of CoimbraNeurology Department, CHUC - Centro Hospitalar e Universitário de Coimbra, CNC- Center for Neuroscience and Cell Biology, University of CoimbraDepartment of Transfusion Medicine, University Medical CenterDepartment of Neurology, Clinical Dementia Center and National Reference Center for CJD Surveillance, University Medical Center GöttingenDepartment of Neurology, Clinical Dementia Center and National Reference Center for CJD Surveillance, University Medical Center GöttingenAbstract 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 non-rapidly 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.https://doi.org/10.1186/s13195-021-00955-9DementiaAlzheimer’s diseaseBiomarkerPlasmaLipocalin 2Neutrophil gelatinase-associated Lipocalin |
| spellingShingle | Peter Hermann Anna Villar-Piqué Matthias Schmitz Christian Schmidt Daniela Varges Stefan Goebel Timothy Bunck Hanna Lindemann Carla Bogner Isabel Santana Inês Baldeiras Joachim Riggert Inga Zerr Franc Llorens Plasma Lipocalin 2 in Alzheimer’s disease: potential utility in the differential diagnosis and relationship with other biomarkers Alzheimer’s Research & Therapy Dementia Alzheimer’s disease Biomarker Plasma Lipocalin 2 Neutrophil gelatinase-associated Lipocalin |
| title | 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_short | 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 |
| topic | Dementia Alzheimer’s disease Biomarker Plasma Lipocalin 2 Neutrophil gelatinase-associated Lipocalin |
| url | https://doi.org/10.1186/s13195-021-00955-9 |
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