Biomarkers of Cerebral Glucose Metabolism and Neurodegeneration in Parkinson’s Disease: A Cerebrospinal Fluid-Based Study

2021 ◽  
pp. 1-8
Author(s):  
Claudio Liguori ◽  
Alessandro Stefani ◽  
Mariana Fernandes ◽  
Rocco Cerroni ◽  
Nicola Biagio Mercuri ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cerebrospinal Fluid ◽  
Cerebral Metabolism ◽  
Tau Proteins ◽  
Csf Biomarkers ◽  
Biomarker Analysis ◽  
Csf Levels ◽  
Lactate Levels ◽  
T Tau

Background: Several biomarkers have been evaluated in Parkinson’s disease (PD); cerebrospinal fluid (CSF) levels of lactate may reflect cerebral metabolism function and CSF amyloid-β42 (Aβ42), total tau (t-tau) and phosphorylated tau (p-tau) concentrations may detect an underlying neurodegenerative process. Objective: CSF levels of lactate, Aβ 42, t-tau, and p-tau were measured in patients with mild to moderate PD. It also assessed CSF levels of dopamine (DA) and its metabolite 3,4-Dihydroxyphenylacetic acid (DOPAC), exploring their relations with the other CSF biomarkers. Methods: 101 drug-naive PD patients and 60 controls were included. Participants underwent clinical assessments and CSF biomarker analysis. Patients were divided into subgroups according to their H&Y stage (PD-1, PD-2, PD-3). Results: PD patients showed higher lactate levels (M = 1.91; p = 0.03) and lower Aβ 42 (M = 595; p <  0.001) and DA levels (M = 0.32; p = 0.04) than controls (Mlactate = 1.72; MAβ42 = 837; MDA = 0.50), while no significant differences were found in t-tau, p-tau and DOPAC concentrations. Considering the subgroup analysis, PD-3 group had higher lactate (M = 2.12) and t-tau levels (M = 333) than both PD-1 (Mlactate = 1.75, p = 0.006; Mt - tau = 176, p = 0.008) and PD-2 groups (Mlactate = 1.91, p = 0.01; Mt - tau = 176, p = 0.03), as well as the controls (Mlactate = 1.72, p = 0.04; Mt - tau = 205, p = 0.04). PD-2 group showed higher lactate levels than PD-1 group (p = 0.04) and controls (p = 0.03). Conclusion: This CSF-based study shows that lactate levels in PD correlated with both clinical disease progression and neurodegeneration biomarkers, such as tau proteins and DA. Further studies should explore the clinical potential of measuring CSF biomarkers for better understanding the role of brain energy metabolism in PD, for research and therapeutic options.

scholarly journals Cerebrospinal Fluid Biomarkers in Multiple System Atrophy Relative to Parkinson’s Disease: A Meta-Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Dan Xie ◽  
Ling Feng ◽  
Hongyan Huang ◽  
Quanzhen Zhao ◽  
Pingping Ning ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cerebrospinal Fluid ◽  
Multiple System Atrophy ◽  
Meta Analysis ◽  
Csf Biomarkers ◽  
Flt3 Ligand ◽  
Cerebrospinal Fluid Biomarkers ◽  
Mean Differences ◽  
T Tau

Objective. To investigate the differences of candidate cerebrospinal fluid (CSF) biomarkers associated with multiple system atrophy (MSA) and Parkinson’s disease (PD). Method. Here, a systematic review and meta-analysis were conducted on studies related to CSF biomarkers associated with MSA and PD obtained from PubMed, Web of Science, Embase, and Cochrane databases. Data were pooled where appropriate and used to calculate standardized mean differences (SMDs) with 95% confidence intervals (CI). Heterogeneity was assessed using the I 2 statistic while Egger’s test was used to test for existing publication bias. Results. MSA patients had higher CSF t-tau ( SMD = 0.41 , 95% CI: 0.10 to 0.72) and YKL-40 ( SMD = 0.63 , 95% CI 0.12 to1.15) as well as DJ-1 ( SMD = 1.05 , 95% CI 0.67 to 1.42) levels than PD patients, while CSF p-tau ( SMD = − 0.17 , 95% CI, -0.31 to -0.02) and Aβ-42 ( SMD = − 0.33 , 95% CI, -0.55 to -0.12) levels in MSA patients were lower than those in PD patients. There were no differences in CSF’s GFAP and Flt3 ligand levels in both MSA and PD patients. Conclusion. The study revealed the differences in CSF biomarker levels between MSA and PD cohorts that can be further explored to clinically distinguish MSA from PD.

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

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).

scholarly journals Alpha-Synuclein Protofibrils in Cerebrospinal Fluid: A Potential Biomarker for Parkinson's Disease

2020 ◽  
Vol 10 (4) ◽  
pp. 1429-1442
Author(s):  
Marianne von Euler Chelpin ◽  
Linda Söderberg ◽  
Johanna Fälting ◽  
Christer Möller ◽  
Marco Giorgetti ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cerebrospinal Fluid ◽  
Single Molecule ◽  
Area Under The Curve ◽  
Corticobasal Degeneration ◽  
Alpha Synuclein ◽  
Cross Reactivity ◽  
Potential Biomarker ◽  
Csf Levels

Background: Currently, there is no established biomarker for Parkinson's disease (PD) and easily accessible biomarkers are crucial for developing disease-modifying treatments. Objective: To develop a novel method to quantify cerebrospinal fluid (CSF) levels of α-synuclein protofibrils (α-syn PF) and apply it to clinical cohorts of patients with PD and atypical parkinsonian disorders. Methods: A cohort composed of 49 patients with PD, 12 with corticobasal degeneration (CBD), 22 with progressive supranuclear palsy, and 33 controls, that visited the memory clinic but had no biomarker signs of Alzheimer’s disease (AD, tau<350 pg/mL, amyloid-beta 42 (Aβ42)>530 pg/mL, and phosphorylated tau (p-tau)<60 pg/mL) was used in this study. The CSF samples were analyzed with the Single molecule array (Simoa) technology. Total α-synuclein (α-syn) levels were analyzed with a commercial ELISA-kit. Results: The assay is specific to α-syn PF, with no cross-reactivity to monomeric α-syn, or the β- and γ-synuclein variants. CSF α-syn PF levels were increased in PD compared with controls (62.1 and 40.4 pg/mL, respectively, p = 0.03), and CBD (62.1 and 34.2 pg/mL, respectively, p = 0.02). The accuracy of predicting PD using α-syn PF is significantly different from controls (area under the curve 0.68, p = 0.0097) with a sensitivity of 62.8% and specificity of 67.7%. Levels of total α-syn were significantly different between the PD and CBD groups (p = 0.04). Conclusion: The developed method specifically quantifies α-syn PF in human CSF with increased concentrations in PD, but with an overlap with asymptomatic elderly controls.

scholarly journals Cerebrospinal Fluid Biomarkers in Parkinson’s Disease: A Critical Overview of the Literature and Meta-Analyses

2020 ◽  
Vol 10 (7) ◽  
pp. 466 ◽  
Author(s):  
Takayuki Katayama ◽  
Jun Sawada ◽  
Kae Takahashi ◽  
Osamu Yahara
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cerebrospinal Fluid ◽  
Biochemical Markers ◽  
Neurodegenerative Disorder ◽  
Meta Analysis ◽  
Analysis Data ◽  
Csf Biomarkers ◽  
Neurofilament Light ◽  
Meta Analyses

Parkinson’s disease (PD) is a common neurodegenerative disorder; however, well-established biochemical markers have not yet been identified. This review article covers several candidate cerebrospinal fluid (CSF) biomarkers for PD based on the recent literature and meta-analysis data. The decrease of α-synuclein in PD is supported by meta-analyses with modest reproducibility, and a decrease of amyloid β42 is seen as a prognostic marker for cognitive decline. Tau, phosphorylated tau (p-tau), and neurofilament light chains have been used to discriminate PD from other neurodegenerative disorders. This article also describes more hopeful biochemical markers, such as neurotransmitters, oxidative stress markers, and other candidate biomarkers.

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

2015 ◽  
Vol 53 (3) ◽  
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.

scholarly journals HIGHER LEVELS OF CEREBROSPINAL FLUID NITRITE AND NITRATE IN LEVODOPA-INDUCED DYSKINESIAS IN PARKINSON’S DISEASE

2020 ◽  
Author(s):  
Bruno L. Santos-Lobato ◽  
Mariza Bortolanza ◽  
Marcelo E. Batalhão ◽  
Ângela V. Pimentel ◽  
Evelin Capellari-Carnio ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cerebrospinal Fluid ◽  
List Type ◽  
Healthy Controls ◽  
Clinical Variables ◽  
Csf Levels ◽  
Nitric Oxide Metabolites

AbstractIntroductionLevodopa-induced dyskinesias (LID) in Parkinson’s disease (PD) are frequent complications, and nitric oxide has a role on its pathophysiology. The present work aims to investigate CSF levels of nitric oxide metabolites nitrite and nitrate (NOx) in patients with PD and LID.MethodsWe measured CSF NOx levels in patients with PD with and without LID, and in healthy controls. The levels of CSF NOx levels were measured by ozone-based chemiluminescence.Results67 participants were enrolled. CSF NOx levels were higher in patients with PD with LID than in healthy controls (Kruskal-Wallis statistics = 7.24, p = 0.02). CSF NOx levels did not correlate with other clinical variables.ConclusionWe reported higher levels of nitric oxide in the CSF of patients with PD and LID.Highlights–Nitric oxide has a role on levodopa-induced dyskinesias in Parkinson’s disease–We measured CSF nitrite and nitrate in Parkinson’s disease patients with dyskinesias–CSF nitrite and nitrate were higher in Parkinson’s disease patients with dyskinesias

scholarly journals Cerebrospinal fluid N-224 tau helps discriminate Alzheimer’s disease from subjective cognitive decline and other dementias

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Claudia Cicognola ◽  
Oskar Hansson ◽  
Philip Scheltens ◽  
Hlin Kvartsberg ◽  
Henrik Zetterberg ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Cerebrospinal Fluid ◽  
Cognitive Decline ◽  
Subjective Cognitive Decline ◽  
Study Cohort ◽  
Not Otherwise Specified ◽  
T Tau

Abstract Background Elevated cerebrospinal fluid (CSF) concentrations of total tau (T-tau) and phosphorylated tau at Thr181 (P-tau181) protein are typical of Alzheimer’s disease (AD). However, the T-tau assay measures only the mid-region of the protein, while tau in CSF is instead composed of a series of fragments. One fragment species in particular, N-224, shows increased levels in AD compared to controls. In this multicentre study, we performed a clinical validation of the N-224 assay in cohorts including patients with subjective cognitive decline (SCD), mild cognitive impairment (MCI), AD, non-AD dementias and controls. Methods Cohorts consisted of 30 SCD and 30 probable AD from the Amsterdam Dementia Cohort (cohort 1) and 539 controls, 195 SCD, 232 MCI, 137 AD and 253 non-AD from the Swedish BioFINDER study (cohort 2). All samples had AD core biomarkers (Aβ42, T-tau, P-tau181) measurements. N-224 was measured with an in-house ultrasensitive Simoa assay. Results N-224 levels were significantly higher in AD compared to SCD (cohort 1: p = 0.003) and in AD compared to all other diagnostic groups in cohort 2 (control, SCD, MCI and non-AD, p < 0.0001). Within the non-AD group, N-224 showed significantly lower concentrations compared to AD in Parkinson’s disease (PD, p < 0.0001), Parkinson’s disease dementia (PDD, p = 0.004), progressive supranuclear palsy (PSP, < 0.0001), multiple system atrophy (MSA, p = 0.002) and parkinsonisms not otherwise specified (NOS, p = 0.007). In cohort 1, higher concentrations of N-224 were associated to lower Mini-Mental State Examination (MMSE) scores (R2 = 0.318, β = 0.564, p ≤ 0.0001) and could accurately identify a pathological (< 24) MMSE score (p < 0.0001, AUC = 0.824). Conclusions N-224 tau can distinguish AD subjects from SCD and can discriminate subgroups of non-AD dementias from AD. Therefore, N-224 may be a useful addition to the tau biomarker toolbox for the study of tau species in CSF and for better understanding disease pathogenesis.

scholarly journals Quantitative Appraisal of Ventricular Cerebrospinal Fluid Biomarkers in Neuropathologically Diagnosed Parkinson's Disease Cases Lacking Alzheimer's Disease Pathology

2013 ◽  
Vol 8 ◽  
pp. BMI.S11422 ◽  
Author(s):  
Chera L. Maarouf ◽  
Thomas G. Beach ◽  
Charles H. Adler ◽  
Michael Malek-Ahmadi ◽  
Tyler A. Kokjohn ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Cerebrospinal Fluid ◽  
Early Stage ◽  
Csf Biomarkers ◽  
Cerebrospinal Fluid Biomarkers ◽  
Proteomic Study ◽  
Quantitative Appraisal

Identifying biomarkers that distinguish Parkinson's disease (PD) from normal control (NC) individuals has the potential to increase diagnostic sensitivity for the detection of early-stage PD. A previous proteomic study identified potential biomarkers in postmortem ventricular cerebrospinal fluid (V-CSF) from neuropathologically diagnosed PD subjects lacking Alzheimer's disease (AD) neuropathology. In the present study, we assessed these biomarkers as well as p-tau181, Aβ42, and S100B by ELISA in PD (n = 43) and NC (n = 49) cases. The p-tau181/Aβ42 ratio and ApoA-1 showed statistically significant differences between groups. Multiple regression analysis demonstrated that p-tau181/Aβ42 had a significant odds ratio: OR = 1.42 (95% confidence interval [CI], 1.12–1.84), P = 0.006. Among the molecules investigated, intriguing correlations were observed that require further investigation. Our results suggest coexistent AD CSF biomarkers within the PD group notwithstanding that it was selected to minimize AD neuropathological lesions.

scholarly journals Mini Review: Correlations of Cognitive Domains With Cerebrospinal Fluid α-Synuclein Levels in Patients With Parkinson's Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Hidetomo Murakami ◽  
Kenjiro Ono ◽  
Tomotaka Shiraishi ◽  
Tadashi Umehara ◽  
Shusaku Omoto ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cerebrospinal Fluid ◽  
Cognitive Performance ◽  
Lewy Bodies ◽  
Executive Dysfunction ◽  
Cognitive Outcome ◽  
The Other ◽  
Cognitive Domains ◽  
Csf Levels

The level of α-synuclein, a component of Lewy bodies, in cerebrospinal fluid (CSF) in Parkinson's disease (PD) has attracted recent attention. Most meta-analyses conclude that CSF levels of α-synuclein are decreased in PD. Patients with PD present with cognitive impairment, including frontal/executive dysfunction in the early phase and later emergence of visuospatial and mnemonic deficits. To examine whether CSF α-synuclein levels reflect the activities of various cognitive domains, we reviewed reports examining the association of these levels with cognitive performance in each domain in PD. Among 13 cross-sectional studies, five showed that a lower CSF α-synuclein level was associated with worse cognitive function. In four of these five reports, frontal/executive function showed this association, suggesting a link of the pathophysiology with Lewy bodies. In three other reports, a higher CSF α-synuclein level was associated with temporal-parieto-occipital cognitive deterioration such as memory. In the other five reports, the CSF α-synuclein level did not correlate with cognitive performance for any domain. In four longitudinal studies, a higher baseline CSF α-synuclein level was associated with a worse cognitive outcome, including cognitive processing speed, visuospatial function and memory in two, but not with any cognitive outcome in the other two. The different associations may reflect the heterogeneous pathophysiology in PD, including different pathogenic proteins, neurotransmitters. Thus, more studies of the association between cognitive domains and CSF levels of pathogenic proteins are warranted.

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