Increased Levels of Hyaluronic Acid in Cerebrospinal Fluid in Patients with Vascular Dementia

Nägga, Katarina; Hansson, Oskar; Westen, Danielle van; Minthon, Lennart; Wennström, Malin

doi:10.3233/jad-141200

Cited by 37 publications

(21 citation statements)

References 37 publications

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“…HA is similarly elevated in gray matter from patients with Alzheimer's disease (AD) [ 37 , 38 ] and the white matter of patients with vascular dementia who have a low burden of AD pathology accompanied by vascular injury consistent with vascular dementia [ 39 ]. In agreement with these findings, Nägga and coworkers [ 40 ] observed significantly increased levels of HA in the cerebrospinal fluid (CSF) from patients with vascular dementia but not AD alone compared with controls. This is consistent with the findings of Laurent and coworkers [ 18 ], who observed elevated HA in the cerebrospinal fluid (CSF) of patients with a number of different neurological diseases.…”

Section: Ha Accumulates In the Damaged Cnssupporting

confidence: 57%

“…This is consistent with the findings of Laurent and coworkers [ 18 ], who observed elevated HA in the cerebrospinal fluid (CSF) of patients with a number of different neurological diseases. Increased levels of HA were also observed in the CSF of individuals with vascular abnormalities determined as significant white matter changes or in patients with previous infarction compared with individuals without these findings [ 40 ]. There was a positive correlation between the levels of HA and the CSF/serum albumin ratio, an indicator of blood-brain barrier integrity, in patients with both vascular dementia and AD.…”

Section: Ha Accumulates In the Damaged Cnsmentioning

confidence: 99%

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Hyaluronan Synthesis, Catabolism, and Signaling in Neurodegenerative Diseases

Sherman

Matsumoto

et al. 2015

International Journal of Cell Biology

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The glycosaminoglycan hyaluronan (HA), a component of the extracellular matrix, has been implicated in regulating neural differentiation, survival, proliferation, migration, and cell signaling in the mammalian central nervous system (CNS). HA is found throughout the CNS as a constituent of proteoglycans, especially within perineuronal nets that have been implicated in regulating neuronal activity. HA is also found in the white matter where it is diffusely distributed around astrocytes and oligodendrocytes. Insults to the CNS lead to long-term elevation of HA within damaged tissues, which is linked at least in part to increased transcription of HA synthases. HA accumulation is often accompanied by elevated expression of at least some transmembrane HA receptors including CD44. Hyaluronidases that digest high molecular weight HA into smaller fragments are also elevated following CNS insults and can generate HA digestion products that have unique biological activities. A number of studies, for example, suggest that both the removal of high molecular weight HA and the accumulation of hyaluronidase-generated HA digestion products can impact CNS injuries through mechanisms that include the regulation of progenitor cell differentiation and proliferation. These studies, reviewed here, suggest that targeting HA synthesis, catabolism, and signaling are all potential strategies to promote CNS repair.

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Section: Ha Accumulates In the Damaged Cnssupporting

confidence: 57%

Section: Ha Accumulates In the Damaged Cnsmentioning

confidence: 99%

Hyaluronan Synthesis, Catabolism, and Signaling in Neurodegenerative Diseases

Sherman

Matsumoto

et al. 2015

International Journal of Cell Biology

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“…Albumin is the most abundant protein in CSF and blood [49], and CSF/serum albumin ratio is commonly used as an indicator of blood-brain barrier integrity [50]. Lower plasma albumin has been reported in AD subjects as compared to healthy controls in a Korean population [51].…”

Section: Discussionmentioning

confidence: 99%

Multifactorial Analysis of a Biomarker Pool for Alzheimer Disease Risk in a North Indian Population

Talwar

Grover

Sinha

et al. 2017

Dement Geriatr Cogn Disord

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Background: Alzheimer disease (AD) is a progressive neurodegenerative disease with a complex multifactorial etiology. Here, we aim to identify a biomarker pool comprised of genetic variants and blood biomarkers as predictor of AD risk. Methods: We performed a case-control study involving 108 cases and 159 non-demented healthy controls to examine the association of multiple biomarkers with AD risk. Results: The APOE genotyping revealed that ε4 allele frequency was significantly high (p value = 0.0001, OR = 2.66, 95% CI 1.58-4.46) in AD as compared to controls, whereas ε2 (p = 0.0430, OR = 0.29, CI 0.07-1.10) was overrepresented in controls. In biochemical assays, significant differences in levels of total copper, free copper, zinc, copper/zinc ratio, iron, epidermal growth factor receptor (EGFR), leptin, and albumin were also observed. The AD risk score (ADRS) as a linear combination of 6 candidate markers involving age, education status, APOE ε4 allele, levels of iron, Cu/Zn ratio, and EGFR was created using stepwise linear discriminant analysis. The area under the ROC curve of the ADRS panel for predicting AD risk was significantly high (AUC = 0.84, p < 0.0001, 95% CI 0.78-0.89, sensitivity = 70.0%, specificity = 83.8%) compared to individual parameters. Conclusion: These findings support the multifactorial etiology of AD and demonstrate the ability of a panel involving 6 biomarkers to discriminate AD cases from non-demented healthy controls.

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“…In addition, biomarkers of the GCX are also being considered as possible indicators of the prognosis and diagnosis of various other diseases. Positive associations with these biomarkers have already been demonstrated for diabetes mellitus [ 57 ], cardiac surgery [ 58 ], Alzheimer disease [ 59 ], hematological disease [ 60 , 61 ], and Crohn’s disease [ 62 ] (Table 2 ). Thus, damage to the GCX, as reflected by the plasma syndecan-1 concentration, is attracting attention in critical care fields.…”

Section: Pathophysiologies Involving the Gcxmentioning

confidence: 99%

Glycocalyx and its involvement in clinical pathophysiologies

2016

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Vascular hyperpermeability is a frequent intractable feature involved in a wide range of diseases in the intensive care unit. The glycocalyx (GCX) seemingly plays a key role to control vascular permeability. The GCX has attracted the attention of clinicians working on vascular permeability involving angiopathies, and several clinical approaches to examine the involvement of the GCX have been attempted. The GCX is a major constituent of the endothelial surface layer (ESL), which covers most of the surface of the endothelial cells and reduces the access of cellular and macromolecular components of the blood to the surface of the endothelium. It has become evident that this structure is not just a barrier for vascular permeability but contributes to various functions including signal sensing and transmission to the endothelium. Because GCX is a highly fragile and unstable layer, the image had been only obtained by conventional transmission electron microscopy. Recently, advanced microscopy techniques have enabled direct visualization of the GCX in vivo, most of which use fluorescent-labeled lectins that bind to specific disaccharide moieties of glycosaminoglycan (GAG) chains. Fluorescent-labeled solutes also enabled to demonstrate vascular leakage under the in vivo microscope. Thus, functional analysis of GCX is advancing. A biomarker of GCX degradation has been clinically applied as a marker of vascular damage caused by surgery. Fragments of the GCX, such as syndecan-1 and/or hyaluronan (HA), have been examined, and their validity is now being examined. It is expected that GCX fragments can be a reliable diagnostic or prognostic indicator in various pathological conditions. Since GCX degradation is strongly correlated with disease progression, pharmacological intervention to prevent GCX degradation has been widely considered. HA and other GAGs are candidates to repair GCX; further studies are needed to establish pharmacological intervention. Recent advancement of GCX research has demonstrated that vascular permeability is not regulated by simple Starling’s law. Biological regulation of vascular permeability by GCX opens the way to develop medical intervention to control vascular permeability in critical care patients.

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Increased Levels of Hyaluronic Acid in Cerebrospinal Fluid in Patients with Vascular Dementia

Cited by 37 publications

References 37 publications

Hyaluronan Synthesis, Catabolism, and Signaling in Neurodegenerative Diseases

Hyaluronan Synthesis, Catabolism, and Signaling in Neurodegenerative Diseases

Multifactorial Analysis of a Biomarker Pool for Alzheimer Disease Risk in a North Indian Population

Glycocalyx and its involvement in clinical pathophysiologies

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