2020
DOI: 10.1038/s41467-020-14373-2
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Cerebrospinal fluid lipocalin 2 as a novel biomarker for the differential diagnosis of vascular dementia

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 dementia… Show more

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Cited by 78 publications
(76 citation statements)
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“…Along the same lines, the progressive increase in the inflammatory and metabolic markers, Lcn2, displayed by aging PP animals, is not reproduced in AD but in the VaD specimen. This finding is in contrast to the previous reports of a rise in Lcn2 protein levels in the hippocampus of severe AD subjects (Naudé et al 2012) and patients with MCI (Choi, Lee, and Suk 2011), but is completely aligned with the recent reported upregulation of Lcn2 in CSF from VaD (n.d.;Llorens et al 2020b). In support of the microvessel damage mediated by Lcn2 (J.-H. Kim et al 2017), 9 months old PP mice report a rise in Cyp1b1, Angptl4 and reduction in Klf4, which all regulate the BB permeability (Sangwung et al 2017;Palenski et al 2013;Huang et al 2011).…”
Section: Reproducibility In Postmortem Tissue From Ad and Vascular Desupporting
confidence: 85%
See 1 more Smart Citation
“…Along the same lines, the progressive increase in the inflammatory and metabolic markers, Lcn2, displayed by aging PP animals, is not reproduced in AD but in the VaD specimen. This finding is in contrast to the previous reports of a rise in Lcn2 protein levels in the hippocampus of severe AD subjects (Naudé et al 2012) and patients with MCI (Choi, Lee, and Suk 2011), but is completely aligned with the recent reported upregulation of Lcn2 in CSF from VaD (n.d.;Llorens et al 2020b). In support of the microvessel damage mediated by Lcn2 (J.-H. Kim et al 2017), 9 months old PP mice report a rise in Cyp1b1, Angptl4 and reduction in Klf4, which all regulate the BB permeability (Sangwung et al 2017;Palenski et al 2013;Huang et al 2011).…”
Section: Reproducibility In Postmortem Tissue From Ad and Vascular Desupporting
confidence: 85%
“…Nevertheless, an increase in Lcn2 has been reported in both AD brains (Dekens et al 2018;Naudé et al 2012) and CSF from vascular dementia patients (Cerebrospinal Fluid) (Llorens et al 2020a) raising the possibility that this molecule can capture a mixed vascular-AD pathology. In line with our PolyI:C model of sterile infection, the increase in Lcn-2 is likely attributed by the production and release by activated microglia, reactive astrocytes, neurons, and endothelial cells in response to inflammatory and infectious insults (Jha et al 2015).…”
Section: Substantial Changes In Brain Metabolism and Inflammationmentioning
confidence: 99%
“…Recently, metabolic syndrome has been regarded as a risk factor for incident vascular dementia. For the differential diagnosis of vascular dementia, the concentration of not only serum LCN-2 but also that of cerebrospinal fluid LCN-2 emerged as a novel biomarker ( Llorens et al, 2020 ). LCN-2 was highly expressed in human atherosclerotic lesions and mouse models of atherosclerosis and myocardial infarction ( Hemdahl et al, 2006 ).…”
Section: Lipocalin-2 (Lcn-2)mentioning
confidence: 99%
“…This finding is in contrast to the previous reports of a rise in Lcn2 protein levels both revealed by immunohistochemistry and immunoblot in the hippocampus of severe AD subjects (Naudé et al 2012) and patients with MCI (Choi, Lee, and Suk 2011), which, in the end, motivated our investigation. Nevertheless, a more recent report has shown that a rise of Lcn2 in CSF facilitates the differential diagnosis of vascular dementia as opposed to AD (Llorens et al 2020). While mixed pathologies in neurodegenerative diseases are not uncommon accounting for 22% of the cases (Custodio et al 2017), the PP model shows a mixed pathology with pronounced neuroinflammation, AD-like proteinopathy, and vascular factors.…”
Section: Reproducibility In Postmortem Tissue From Ad Patientsmentioning
confidence: 99%