Cerebrospinal Fluid Biomarkers in Spinocerebellar Ataxia: A Pilot Study

Neurodegenerative diseases, including the spinocerebellar ataxias (SCA), would benefit from the identification of reliable biomarkers that could serve as disease subtype-specific and stage-specific indicators for the development and monitoring of treatments. We analyzed the cerebrospinal fluid (CSF) level of tau,α-synuclein, DJ-1, and glial fibrillary acidic protein (GFAP), proteins previously associated with neurodegenerative processes, in patients with the autosomal dominant SCA1, SCA2, and SCA6, and the sporadic disease multiple system atrophy, cerebellar type (MSA-C), compared with age-matched controls. We estimated disease severity using the Scale for the Assessment and Rating of Ataxia (SARA). Most proteins measured trended higher in disease versus control group yet did not reach statistical significance. We found the levels of tau in both SCA2 and MSA-C patients were significantly higher than control. We found thatα-synuclein levels were lower with higher SARA scores in SCA1 and tau levels were higher with greater SARA in MSA-C, although this final correlation did not reach statistical significance after post hoc correction. Additional studies with larger sample sizes are needed to improve the power of these studies and validate the use of CSF biomarkers in SCA and MSA-C.

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Cerebrospinal fluid levels of 5-hydroxyindoleacetic acid in Parkinson’s disease and atypical parkinsonian syndromes

Neurodegenerative Diseases ◽

10.1159/000520302 ◽

2021 ◽

Author(s):

Michaela Kaiserova ◽

Monika Chudackova ◽

Hana Prikrylova Vranova ◽

Katerina Mensikova ◽

Anetta Kastelikova ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cerebrospinal Fluid ◽

Statistical Significance ◽

Corticobasal Degeneration ◽

Control Group ◽

Csf Biomarkers ◽

Parkinsonian Syndromes ◽

Significant Difference ◽

Hydroxyindoleacetic Acid

Background: Various cerebrospinal fluid (CSF) biomarkers are studied in Parkinson’s disease (PD) and atypical parkinsonian syndromes (APS). Several studies found reduced 5-hydroxyindoleacetic acid (5-HIAA), the main serotonin metabolite, in PD. There is little evidence regarding its levels in APS. Methods: We measured 5-HIAA in the CSF of 90 PD patients, 16 MSA patients, 26 progressive supranuclear palsy (PSP) patients, 11 corticobasal degeneration (CBD) patients, and 31 controls. We also compared the values in depressed and non-depressed patients. Results: There was a statistically significant difference in CSF 5-HIAA in PD and MSA compared to the control group (median in PD 15.8 µg/l, in MSA 13.6 µg/l vs. 24.3 µg/l in controls; P=0.0008 in PD, P=0.006 in MSA). There was no statistically significant difference in CSF 5-HIAA in PSP and CBD compared to the control group (median in PSP 22.7 µg/l, in CBD 18.7 µg/l vs. 24.3 µg/l in controls; P= 1 in both PSP and CBD). CSF 5-HIAA levels were lower in PD patients with depression compared to PD patients without depression (median 8.34 vs. 18.48, P<0.0001). Conclusions: CSF 5-HIAA is decreased in PD and MSA. The CSF 5-HIAA levels in PSP and CBS did not differ from those of the control group. There was a tendency toward lower CSF 5-HIAA in MSA than in PD, however, the results did not reach statistical significance. These results may be explained by more severe damage of the serotonergic system in synucleinopathies (PD, MSA) than in tauopathies (PSP, CBS).

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The Relationships between HIV-1 Infection, History of Methamphetamine Use Disorder, and Soluble Biomarkers in Blood and Cerebrospinal Fluid

Viruses ◽

10.3390/v13071287 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1287

Author(s):

T. Walter ◽

Jennifer Iudicello ◽

Debra Cookson ◽

Donald Franklin ◽

Bin Tang ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Immune System ◽

Public Health Problem ◽

Control Group ◽

Csf Biomarkers ◽

Immune System Dysfunction ◽

Immune Biomarkers ◽

Plasma Factor ◽

History Of ◽

Hiv 1

Methamphetamine (METH) use disorder is highly prevalent among people with HIV (PWH) and is a significant public health problem. HIV and METH use are each associated with immune system dysfunction; however, the combined effects on the immune system are poorly understood. This cross-sectional project measured soluble immune biomarkers in plasma and cerebrospinal fluid (CSF) collected from a control group, people with a history of a METH use disorder (METH+), PWH with no history of METH use disorder (HIV+), and PWH with a history of METH use disorder (HIV+/METH+). HIV, METH, and immune dysfunction can also be associated with affective and cognitive deficits, so we characterized mood and cognition in our participants. Two factor analyses were performed for the plasma and CSF biomarkers. Plasma IL-8, Ccl2, VEGF, and 8-isoprostane loaded onto one factor that was highest in the HIV+/METH+ group (p < 0.047) reflecting worse inflammation, vascular injury, and oxidative stress. This plasma factor was also negatively correlated with delayed recall (R = −0.49, p = 0.010), which was worst in the HIV+/METH+ group (p = 0.030 compared to the control group). Overall, these data implicate that combined HIV-1 infection and METH use may exacerbate inflammation, leading to worse cognition.

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Antimicrobial effect of methylene blue formulations with oxygen carrier at different pHs: preliminary study

Brazilian Dental Science ◽

10.14295/bds.2019.v22i1.1635 ◽

2019 ◽

Vol 22 (1) ◽

pp. Process

Author(s):

Jessica Klöckner Knorst ◽

Gabriela Scarton Barriquello ◽

Marcos Antônio Villetti ◽

Roberto Christ Vianna Santos ◽

Karla Zanini Kantorski

Keyword(s):

Methylene Blue ◽

Pseudomonas Aeruginosa ◽

Photodynamic Therapy ◽

Oxygen Carrier ◽

Statistical Significance ◽

Antimicrobial Effect ◽

Control Group ◽

Preliminary Study ◽

Post Hoc ◽

Multispecies Biofilms

Objective: Evaluate methylene blue (MB) formulations containing oxygen carrier at different pHs in antimicrobial photodynamic therapy (aPDT). Material and Methods: Biofilms of Pseudomonas aeruginosa PA01 formed over acrylics specimens during five days were treated with aPDT using different formulations: MB/pH 7.4; MB/pH 5.6; MB/carrier pH 7.4; MB/carrier pH 5.6. Biofilms not exposed to treatment were used as a control. Blind examiner for the experimental groups performed the counting of colonies per ml suspension (CFU/ml). Two-way ANOVA was used to determine the effect of factors solvent (carrier vs water) and pH (7.4 vs 5.6). One-way ANOVA and post-hoc Tukey’s test was used to evaluate differences among the five groups (control; MB/carrier pH 7.4; MB pH 7.4; MB/carrier pH 5.6; MB pH 5.6). The Statistics 8.0 software was used (P<0.05). Results: All of photodynamic therapy groups showed significant reduction in P. aeruginosa compared to the control group. The solvent factor was not significant (P=0.18), while the pH factor presented statistical significance (P=0.01). When the carrier was used, MB formulation at pH 7.4 presented a statistically greater reduction of P. aeruginosa than the formulation with pH 5.6. Conclusion: The PDT using methylene blue formulations with oxygen carrier demonstrated potential for the treatment of localized infections by P. aeruginosa. MB formulations with oxygen carrier and pH 7.4 resulted in higher antimicrobial effect and should be considered for future studies with multispecies biofilms. KeywordsAntimicrobial photodynamic therapy; biofilm; laser; Pseudomonas aeruginosa.

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Brevican and Neurocan Peptides as Potential Cerebrospinal Fluid Biomarkers for Differentiation Between Vascular Dementia and Alzheimer’s Disease

Journal of Alzheimer s Disease ◽

10.3233/jad-201039 ◽

2020 ◽

pp. 1-13

Author(s):

Karolina Minta ◽

Gunnar Brinkmalm ◽

Erik Portelius ◽

Per Johansson ◽

Johan Svensson ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cerebrospinal Fluid ◽

Vascular Dementia ◽

Extracellular Enzymes ◽

Control Group ◽

Healthy Controls ◽

Clear Trend ◽

Cerebrospinal Fluid Biomarkers

Background: Brevican and neurocan are central nervous system-specific extracellular matrix proteoglycans. They are degraded by extracellular enzymes, such as metalloproteinases. However, their degradation profile is largely unexplored in cerebrospinal fluid (CSF). Objective: The study aim was to quantify proteolytic peptides derived from brevican and neurocan in human CSF of patients with Alzheimer’s disease (AD) and vascular dementia (VaD) compared with controls. Methods: The first cohort consisted of 75 individuals including 25 patients with AD, 7 with mild cognitive impairment (MCI) diagnosed with AD upon follow-up, 10 patients with VaD or MCI diagnosed with VaD upon follow-up, and 33 healthy controls and cognitively stable MCI patients. In the second cohort, 31 individuals were included (5 AD patients, 14 VaD patients and 12 healthy controls). Twenty proteolytic peptides derived from brevican (n = 9) and neurocan (n = 11) were quantified using high-resolution parallel reaction monitoring mass spectrometry. Results: In the first cohort, the majority of CSF concentrations of brevican and neurocan peptides were significantly decreased inVaDas compared withADpatients (AUC = 0.83.0.93, p≤0.05) and as compared with the control group (AUC = 0.79.0.87, p ≤ 0.05). In the second cohort, CSF concentrations of two brevican peptides (B87, B156) were significantly decreased in VaD compared with AD (AUC = 0.86.0.91, p ≤ 0.05) and to controls (AUC = 0.80.0.82, p ≤ 0.05), while other brevican and neurocan peptides showed a clear trend to be decreased in VaD compared with AD (AUC = 0.64.80, p > 0.05). No peptides differed between AD and controls. Conclusion: Brevican and neurocan peptides are potential diagnostic biomarkers for VaD, with ability to separate VaD from AD.

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Cerebrospinal fluid neopterin as a biomarker of neuroinflammatory diseases

Scientific Reports ◽

10.1038/s41598-020-75500-z ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Marta Molero-Luis ◽

Didac Casas-Alba ◽

Gabriela Orellana ◽

Aida Ormazabal ◽

Cristina Sierra ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Discriminant Analysis ◽

Bacterial Infections ◽

Pediatric Patients ◽

Canonical Discriminant Analysis ◽

Control Group ◽

Csf Biomarkers ◽

Molecular Testing ◽

Respiratory Pathogens

Abstract The elevation of neopterin in cerebrospinal fluid (CSF) has been reported in several neuroinflammatory disorders. However, it is not expected that neopterin alone can discriminate among different neuroinflammatory etiologies. We conducted an observational retrospective and case–control study to analyze the CSF biomarkers neopterin, total proteins, and leukocytes in a large cohort of pediatric patients with neuroinflammatory disorders. CSF samples from 277 subjects were included and classified into four groups: Viral meningoencephalitis, bacterial meningitis, acquired immune-mediated disorders, and patients with no-immune diseases (control group). CSF neopterin was analyzed with high-performance liquid chromatography. Microbiological diagnosis included bacterial CSF cultures and several specific real-time polymerase chain reactions. Molecular testing for multiple respiratory pathogens was also included. Antibodies against neuronal and glial proteins were tested. Canonical discriminant analysis of the three biomarkers was conducted to establish the best discriminant functions for the classification of the different clinical groups. Model validation was done by biomarker analyses in a new cohort of 95 pediatric patients. CSF neopterin displayed the highest values in the viral and bacterial infection groups. By applying canonical discriminant analysis, it was possible to classify the patients into the different groups. Validation analyses displayed good results for neuropediatric patients with no-immune diseases and for viral meningitis patients, followed by the other groups. This study provides initial evidence of a more efficient approach to promote the timely classification of patients with viral and bacterial infections and acquired autoimmune disorders. Through canonical equations, we have validated a new tool that aids in the early and differential diagnosis of these neuroinflammatory conditions.

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Cerebrospinal Fluid Biomarkers in Idiopathic Normal Pressure Hydrocephalus

International Journal of Alzheimer s Disease ◽

10.4061/2011/312526 ◽

2011 ◽

Vol 2011 ◽

pp. 1-6 ◽

Cited By ~ 11

Author(s):

Ville Leinonen ◽

Lata G. Menon ◽

Rona S. Carroll ◽

Donna Dello Iacono ◽

Jeremy Grevet ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Normal Pressure Hydrocephalus ◽

Normal Pressure ◽

Idiopathic Normal Pressure Hydrocephalus ◽

Csf Biomarkers ◽

Cerebrospinal Fluid Biomarkers ◽

In The Beginning ◽

Related Proteins ◽

Selection Of Patients ◽

Selection Of

The diagnosis of idiopathic normal pressure hydrocephalus (iNPH) is still challenging. Alzheimer's disease (AD), along with vascular dementia, the most important differential diagnosis for iNPH, has several potential cerebrospinal fluid (CSF) biomarkers which might help in the selection of patients for shunt treatment. The aim of this study was to compare a battery of CSF biomarkers including well-known AD-related proteins with CSF from patients with suspected iNPH collected from the external lumbar drainage test (ELD). A total of 35 patients with suspected iNPH patients were evaluated with ELD. CSF was collected in the beginning of the test, and the concentrations of total tau, ptau181, Aβ42, NFL, TNF-α, TGFβ1, and VEGF were analysed by ELISA. Twenty-six patients had a positive ELD result—that is, their gait symptoms improved; 9 patients had negative ELD. The levels of all analyzed CSF biomarkers were similar between the groups and none of them predicted the ELD result in these patients. Contrary to expectations lumbar CSF TNF-αconcentration was low in iNPH patients.

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Integrated proteomics reveals brain-based cerebrospinal fluid biomarkers in asymptomatic and symptomatic Alzheimer’s disease

Science Advances ◽

10.1126/sciadv.aaz9360 ◽

2020 ◽

Vol 6 (43) ◽

pp. eaaz9360 ◽

Cited By ~ 1

Author(s):

Lenora Higginbotham ◽

Lingyan Ping ◽

Eric B. Dammer ◽

Duc M. Duong ◽

Maotian Zhou ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cerebrospinal Fluid ◽

Wide Spectrum ◽

Csf Biomarkers ◽

Protein Biomarkers ◽

Cerebrospinal Fluid Biomarkers ◽

Brain Proteome ◽

The Brain ◽

Underlying Pathophysiology

Alzheimer’s disease (AD) lacks protein biomarkers reflective of its diverse underlying pathophysiology, hindering diagnostic and therapeutic advancements. Here, we used integrative proteomics to identify cerebrospinal fluid (CSF) biomarkers representing a wide spectrum of AD pathophysiology. Multiplex mass spectrometry identified ~3500 and ~12,000 proteins in AD CSF and brain, respectively. Network analysis of the brain proteome resolved 44 biologically diverse modules, 15 of which overlapped with the CSF proteome. CSF AD markers in these overlapping modules were collapsed into five protein panels representing distinct pathophysiological processes. Synaptic and metabolic panels were decreased in AD brain but increased in CSF, while glial-enriched myelination and immunity panels were increased in brain and CSF. The consistency and disease specificity of panel changes were confirmed in >500 additional CSF samples. These panels also identified biological subpopulations within asymptomatic AD. Overall, these results are a promising step toward a network-based biomarker tool for AD clinical applications.

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Targeted metabolomic profiling of cerebrospinal fluid from patients with progressive multifocal leukoencephalopathy

PLoS ONE ◽

10.1371/journal.pone.0242321 ◽

2020 ◽

Vol 15 (11) ◽

pp. e0242321

Author(s):

Yi Luo ◽

Nora Möhn ◽

Amani Al-Mekhlafi ◽

Sven Schuchardt ◽

Thomas Skripuletz ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Progressive Multifocal Leukoencephalopathy ◽

Demyelinating Disease ◽

Statistical Significance ◽

Virus Detection ◽

Normal Pressure ◽

Csf Biomarkers ◽

Diagnostic Biomarkers ◽

Metabolomic Profiling ◽

The Central Nervous System

Progressive multifocal leukoencephalopathy (PML), caused by JC polyomavirus, is a demyelinating disease of the central nervous system that primarily affects oligodendrocytes. It can cause significant morbidity and mortality. An early diagnosis is of high relevance as timely immune reconstitution is essential. However, diagnosis can be challenging if virus detection via cerebrospinal fluid (CSF) PCR remains negative. Hence, identifying CSF biomarkers for this disease is of crucial importance. We applied a targeted metabolomic screen to CSF from 23 PML patients and eight normal pressure hydrocephalus (NPH) patients as controls. Out of 188 potentially detectable metabolites, 48 (13 amino acids, 4 biogenic amines, 1 acylcarnitine, 21 phosphatidylcholines, 8 sphingolipids, and the sum of hexoses) passed the quality screen and were included in the analyses. Even though there was a tendency towards lower concentrations in PML (mostly of phosphatidylcholines and sphingomyelins), none of the differences between PML and controls in individual metabolite concentrations reached statistical significance (lowest p = 0.104) and there were no potential diagnostic biomarkers (highest area under the ROC curve 0.68). Thus, CSF metabolite changes in PML are likely subtle and possibly larger group sizes and broader metabolite screens are needed to identify potential CSF metabolite biomarkers for PML.

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Cerebrospinal Fluid Biomarkers for Dementia with Lewy Bodies

International Journal of Alzheimer s Disease ◽

10.4061/2010/536538 ◽

2010 ◽

Vol 2010 ◽

pp. 1-17 ◽

Cited By ~ 7

Author(s):

Elizabeta B. Mukaetova-Ladinska ◽

Rachael Monteith ◽

Elaine K. Perry

Keyword(s):

Cerebrospinal Fluid ◽

Dementia With Lewy Bodies ◽

Lewy Bodies ◽

Low Frequency ◽

Csf Biomarkers ◽

Term Care ◽

Clinical Criteria ◽

Cerebrospinal Fluid Biomarkers ◽

The Uk ◽

T Tau

More than 750,000 of the UK population suffer from some form of cognitive impairment and dementia. Of these, 5–20% will have Dementia with Lewy Bodies (DLB). Clinico-pathological studies have shown that it is the low frequency of DLB clinical core features that makes the DLB diagnosis hardly recognisable during life, and easily misdiagnosed for other forms of dementia. This has an impact on the treatment and long-term care of the affected subjects. Having a biochemical test, based on quantification of a specific DLB biomarker within Cerebrospinal Fluid (CSF) could be an effective diagnostic method to improve the differential diagnosis. Although some of the investigated DLB CSF biomarkers are well within the clinical criteria for sensitivity and specificity (90%), they all seem to be confounded by the contradictory data for each of the major groups of biomarkers (-synuclein, tau and amyloid proteins). However, a combination of CSF measures appear to emerge, that may well be able to differentiate DLB from other dementias: -synuclein reduction in early DLB, a correlation between CSF -synuclein and A42 measures (characteristic for DLB only), and t-tau and p-tau181 profile (differentiating AD from DLB).

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Role of cerebrospinal fluid biomarkers to predict conversion to dementia in patients with mild cognitive impairment: a clinical cohort study

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2014-0414 ◽

2015 ◽

Vol 53 (3) ◽

Cited By ~ 7

Author(s):

Manuela Tondelli ◽

Roberta Bedin ◽

Annalisa Chiari ◽

Maria Angela Molinari ◽

Guendalina Bonifacio ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Csf Biomarkers ◽

Neuropsychological Evaluation ◽

Neurological Assessment ◽

Blood Tests ◽

Clinical Cohort ◽

Cerebrospinal Fluid Biomarkers ◽

Csf Levels ◽

T Tau

AbstractCerebrospinal fluid (CSF) levels assessment of AβA group of 71 MCI patients underwent neurological assessment, extended neuropsychological evaluation, routine blood tests, ApoE determination, and lumbar puncture to dose t-tau, p-tauBaseline AβOur results confirm the key role of CSF biomarkers in predicting patient conversion from MCI to dementia. The study suggests that CSF biomarkers may also be reliable in a real world clinical setting.

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