Association between lipocalin-2 and mild cognitive impairment or dementia: A systematic review and meta-analysis of population-based evidence

Li, Xiuwen; Wang, Xiaojie; Guo, Lan; Wu, Keying; Wang, Li; Rao, Lu; Liu, Xinjian; Kang, Chenyao; Jiang, Bin; Li, Qian; Li, Huling; He, Fenghua; Lu, Ciyong

doi:10.1016/j.arr.2023.101984

Cited by 3 publications

(1 citation statement)

References 44 publications

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“…We found that plasma LCN2 levels were negatively correlated with MoCA scores in PD patients. LCN2 may mediate cognitive dysfunction by regulating neuroinflammation, damaging neurons, and inducing synaptic dysfunction (Li et al, 2023). Inflammation has been proven to play a role in cognitive decline (Yaffe et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Increased plasma lipocalin‐2 levels are associated with nonmotor symptoms and neuroimaging features in patients with Parkinson's disease

Fan,

Li,

et al. 2024

J of Neuroscience Research

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Lipocalin‐2 (LCN2) is essential for the regulation of neuroinflammation and cellular uptake of iron. This study aimed to evaluate plasma LCN2 levels and explore their correlation with clinical and neuroimaging features in Parkinson's disease (PD) patients. Enzyme‐linked immunosorbent assay (ELISA) was used to measure plasma LCN2 levels in 120 subjects. Evaluation of motor symptoms and nonmotor symptoms in PD patients was assessed by the associated scales. Voxel‐based morphometry (VBM) was used to evaluate brain volume alterations, and quantitative susceptibility mapping (QSM) was used to quantitatively analyze brain iron deposition in 46 PD patients. Plasma LCN2 levels were significantly higher in PD patients than those in healthy controls. LCN2 levels were negatively correlated with Montreal Cognitive Assessment (MoCA) scores, total brain gray matter volume (GMV), and GMV/total intracranial volume (TIV) ratio, but positively correlated with Hamilton Anxiety Rating Scale (HAMD) scores and mean QSM values of the bilateral substantial nigra (SN). Receiver operating characteristic (ROC) curves confirmed that plasma LCN2 levels had good predictive accuracy for PD. The results suggest that plasma LCN2 levels have potential as a biomarker for the diagnosis of PD. LCN2 may be a therapeutic target for neuroinflammation and brain iron deposition.

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Section: Discussionmentioning

confidence: 99%

Increased plasma lipocalin‐2 levels are associated with nonmotor symptoms and neuroimaging features in patients with Parkinson's disease

Fan,

Li,

et al. 2024

J of Neuroscience Research

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Plasmodium knowlesiinfection is associated with elevated circulating biomarkers of brain injury and endothelial activation

Bertran-Cobo,

Dumont,

Noordin

et al. 2024

Preprint

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Introduction: Malaria remains a major public health concern with substantial morbidity and mortality worldwide. In Malaysia, the emergence of Plasmodium knowlesi has led to a surge in zoonotic malaria cases and deaths in recent years. Signs of cerebral involvement have been observed in a non-comatose, fatal case of severe knowlesi infection, but the potential impact of this malaria species on the brain remains underexplored. To address this gap, we investigated circulating levels of brain injury, inflammation, and vascular biomarkers in a cohort of knowlesi-infected patients and controls. Methods: Archived plasma samples from 19 patients with confirmed symptomatic knowlesi infection and 19 healthy, age-matched controls from Peninsular Malaysia were analysed. A total of 52 plasma biomarkers of brain injury, inflammation, and vascular activation were measured using Luminex and SIMOA assays. Wilcoxon tests were used to examine group differences, and biomarker profiles were explored through hierarchical clustering heatmap analysis. Results: Bonferroni-corrected analyses revealed significantly elevated brain injury biomarker levels in knowlesi-infected patients, including S100B (p<0.0001), Tau (p=0.0007), UCH-L1 (p<0.0001), αSyn (p<0.0001), Park7 (p=0.0006), NRGN (p=0.0022), and TDP-43 (p=0.005). Compared to controls, levels were lower in the infected group for BDNF (p<0.0001), CaBD (p<0.0001), CNTN1 (p<0.0001), NCAM-1 (p<0.0001), GFAP (p=0.0013), and KLK6 (p=0.0126). Hierarchical clustering revealed distinct group profiles for circulating levels of brain injury and vascular activation biomarkers. Conclusions: Our findings highlight for the first time the impact of Plasmodium knowlesi infection on the brain, with distinct alterations in cerebral injury and endothelial activation biomarker profiles compared to healthy controls. Further studies are warranted to investigate the pathophysiology and clinical significance of these altered surrogate markers, through both neuroimaging and long-term neurocognitive assessments.

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Associations between Microglia and Astrocytic Proteins and Tau Biomarkers across the Continuum of Alzheimer’s Disease

Doroszkiewicz,

Kulczyńska-Przybik,

Dulewicz

et al. 2024

IJMS

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Recent investigations implicate neuroinflammatory changes, including astrocyte and microglia activation, as crucial in the progression of Alzheimer’s disease (AD) Thus, we compared selected proteins reflecting neuroinflammatory processes to establish their connection to AD pathologies. Our study, encompassing 80 subjects with (n = 42) AD, (n = 18) mild cognitive impairment (MCI) and (n = 20) non-demented controls compares the clinical potential of tested molecules. Using antibody-based methods, we assessed concentrations of NGAL, CXCL-11, sTREM1, and sTREM2 in cerebrospinal fluid (CSF). Proinflammatory proteins, NGAL, and CXCL-11 reached a peak in the early stage of the disease and allowed for the identification of patients with MCI. Furthermore, the concentration of the anti-inflammatory molecule sTREM2 was highest in the more advanced stage of the disease and permitted differentiation between AD and non-demented controls. Additionally, sTREM2 was biochemically linked to tau and pTau in the AD group. Notably, NGAL demonstrated superior diagnostic performance compared to classical AD biomarkers in discriminating MCI patients from controls. These findings suggest that proteins secreted mainly through microglia dysfunction might play not only a detrimental but also a protective role in the development of AD pathology.

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Association between lipocalin-2 and mild cognitive impairment or dementia: A systematic review and meta-analysis of population-based evidence

Cited by 3 publications

References 44 publications

Increased plasma lipocalin‐2 levels are associated with nonmotor symptoms and neuroimaging features in patients with Parkinson's disease

Increased plasma lipocalin‐2 levels are associated with nonmotor symptoms and neuroimaging features in patients with Parkinson's disease

Plasmodium knowlesiinfection is associated with elevated circulating biomarkers of brain injury and endothelial activation

Associations between Microglia and Astrocytic Proteins and Tau Biomarkers across the Continuum of Alzheimer’s Disease

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