scholarly journals VGF Peptides in Cerebrospinal Fluid of Patients with Dementia with Lewy Bodies

2019 ◽  
Vol 20 (19) ◽  
pp. 4674 ◽  
Author(s):  
Inger van Steenoven ◽  
Barbara Noli ◽  
Cristina Cocco ◽  
Gian-Luca Ferri ◽  
Patrick Oeckl ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Cognitive Decline ◽  
Analytical Methods ◽  
Dementia With Lewy Bodies ◽  
Lewy Bodies ◽  
Disease Stage ◽  
Selected Reaction Monitoring ◽  
Csf Biomarkers ◽  
Potential Biomarker ◽  
Proteomic Study

In a previous proteomic study, we identified the neurosecretory protein VGF (VGF) as a potential biomarker for dementia with Lewy bodies (DLB). Here, we extended the study of VGF by comparing levels in cerebrospinal fluid (CSF) from 44 DLB patients, 20 Alzheimer’s disease (AD) patients, and 22 cognitively normal controls selected from the Amsterdam Dementia Cohort. CSF was analyzed using two orthogonal analytical methods: (1) In-house-developed quantitative ELISA and (2) selected reaction monitoring (SRM). We further addressed associations of VGF with other CSF biomarkers and cognition. VGF levels were lower in CSF from patients with DLB compared to either AD patients or controls. VGF was positively correlated with CSF tau and α-synuclein (0.55 < r < 0.75), but not with Aβ1-42. In DLB patients, low VGF levels were related to a more advanced cognitive decline at time of first presentation, whereas high levels of VGF were associated with steeper subsequent longitudinal cognitive decline. Hence, CSF VGF levels were lower in DLB compared to both AD and controls across different analytical methods. The strong associations with cognitive decline further points out VGF as a possible disease stage or prognostic marker for DLB.

scholarly journals Cerebrospinal Fluid Biomarkers for Dementia with Lewy Bodies

2010 ◽  
Vol 2010 ◽  
pp. 1-17 ◽  
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).

scholarly journals Kynurenic Acid Levels in Cerebrospinal Fluid from Patients with Alzheimer's Disease or Dementia with Lewy Bodies

2014 ◽  
Vol 7 ◽  
pp. IJTR.S13958 ◽  
Author(s):  
Malin Wennström ◽  
Henrietta M Nielsen ◽  
Funda Orhan ◽  
Elisabet Londos ◽  
Lennart Minthon ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Cognitive Decline ◽  
Cognitive Functions ◽  
Dementia With Lewy Bodies ◽  
Kynurenic Acid ◽  
Lewy Bodies ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1

Kynurenic acid (KYNA) is implicated in cognitive functions. Altered concentrations of the compound are found in serum and cerebrospinal fluid (CSF) of patients with Alzheimer's disease (AD). Further studies to determine whether KYNA serves as a biomarker for cognitive decline and dementia progression are required. In this study, we measured CSF KYNA levels in AD patients (n = 19), patients with dementia with Lewy bodies (DLB) (n = 18), and healthy age-matched controls (Ctrls)) (n = 20) to further explore possible correlations between KYNA levels, cognitive decline, and well-established AD and inflammatory markers. Neither DLB patients nor AD patients showed significantly altered CSF KYNA levels compared to Ctrls. However, female AD patients displayed significantly higher KYNA levels compared to male AD patients, a gender difference not seen in the Ctrl or DLB group. Levels of KYNA significantly correlated with the AD-biomarker P-tau and the inflammation marker soluble intercellular adhesion molecule-1 (sICAM-1) in the AD patient group. No associations between KYNA and cognitive functions were found. Our study shows that, although KYNA was not associated with cognitive decline in AD or DLB patients, it may be implicated in AD-related hyperphosphorylation of tau and inflammation. Further studies on larger patient cohorts are required to understand the potential role of KYNA in AD and DLB.

scholarly journals Cerebrospinal Fluid, Imaging, and Physiological Biomarkers in Dementia With Lewy Bodies

2019 ◽  
Vol 34 (7-8) ◽  
pp. 421-432
Author(s):  
Ioannis Mavroudis ◽  
Foivos Petridis ◽  
Dimitrios Kazis
Keyword(s):  
Cerebrospinal Fluid ◽  
Alzheimer Disease ◽  
Dementia With Lewy Bodies ◽  
Autonomic Function ◽  
Neurodegenerative Disorder ◽  
Lewy Bodies ◽  
Behavioral Changes ◽  
Western World ◽  
Csf Biomarkers ◽  
Fluid Imaging

Dementia with Lewy bodies is a progressive neurodegenerative disorder, clinically characterized by gradual cognitive impairment and fluctuating cognition, behavioral changes and recurrent visual hallucinations, and autonomic function and movement symptoms in the type of parkinsonism. It is the second most common type of dementia in the Western world after Alzheimer disease. Over the last 20 years, many neurophysiological, neuroimaging, and cerebrospinal fluid (CSF) biomarkers have been described toward a better discrimination between dementia with Lewy bodies, Alzheimer disease, and other neurodegenerative conditions.In the present review, we aim to describe the neurophysiological, imaging, and CSF biomarkers in dementia with Lewy bodies and to question whether they could be reliable tools for the clinical practice.

Validation of a new assay for α-synuclein detection in cerebrospinal fluid

2017 ◽  
Vol 55 (2) ◽  
Author(s):  
Marthe Gurine Førland ◽  
Annika Öhrfelt ◽  
Linn Silje Oftedal ◽  
Ole-Bjørn Tysnes ◽  
Jan Petter Larsen ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Neurodegenerative Diseases ◽  
Dementia With Lewy Bodies ◽  
Limit Of Detection ◽  
Lewy Bodies ◽  
High Sensitivity ◽  
Cross Reactivity ◽  
Additional Method ◽  
Potential Biomarker ◽  
Assay Protocol

AbstractBackground:Abnormal α-synuclein aggregation and deposition is the pathological hallmark of Parkinson’s disease (PD) and dementia with Lewy bodies (DLB), but is also found in Alzheimer disease (AD). Therefore, there is a gaining interest in α-synuclein in cerebrospinal fluid (CSF) as potential biomarker for these neurodegenerative diseases. To broaden the available choices of α-synuclein measurement in CSF, we developed and validated a new assay for detecting total α-synuclein.Methods:This novel ELISA uses commercially available antibodies and is based on electrochemiluminescence technology. The assay protocol is straightforward, with short and simple incubation steps, and requires only small amounts of CSF. We validated this assay for precision, parallelism, dilution linearity, specificity, and spike recovery. We further compared it to the newly validated α-synuclein assay from BioLegend by analyzing a set of 50 CSF samples with both assays.Results:The new assay quantifies α-synuclein in CSF with a lower limit of detection of 36.3 pg/mL and shows no cross-reactivity with human β- and γ-synuclein. Results of dilution linearity, parallelism, spike recovery, and precision classify this assay as well suited for α-synuclein detection in human CSF samples.Conclusions:We present a novel assay based on freely available components to quantify total α-synuclein in CSF as an additional method for α-synuclein as a biomarker in neurodegenerative diseases. The assay convinces with its simple and convenient protocol paired with high sensitivity.

scholarly journals Cerebrospinal fluid α synuclein concentrations in patients with positive AD biomarkers and extrapyramidal symptoms

2021 ◽  
Author(s):  
Izabela Winkel ◽  
Natalia Ermann ◽  
Agnieszka Żelwetro ◽  
Bożydar Sambor ◽  
Barbara Mroczko ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Lewy Bodies ◽  
Average Concentration ◽  
Extrapyramidal Symptoms ◽  
Csf Biomarkers ◽  
Neurodegenerative Process ◽  
Potential Biomarker ◽  
Dementia Diagnostics ◽  
Pathophysiologic Mechanisms

AbstractExtrapyramidal symptoms (EP) are not uncommon in Alzheimer’s Disease (AD); when present, they negatively influence the course of the disorder. A large proportion of AD patients shows concomitant Lewy bodies’ pathology post mortem. Total α Synuclein (αSyn) concentrations are frequently increased in the cerebrospinal fluid (CSF) of AD patients, but are decreased in Parkinson’s Disease (PD) and Dementia with Lewy Bodies (DLB). αSyn CSF concentrations in AD patients with EP (EP+) have not been reported so far. αSyn and the four Neurochemical Dementia Diagnostics (NDD) CSF biomarkers, (Aβ1-42, Aβ42/40, Tau, and pTau181), interpreted according to the Erlangen Score algorithm, were measured in patients with positive NDD results and presence of extrapyramidal symptoms (NDD + / EP+; n = 26), in patients with positive NDD results and absence of extrapyramidal symptoms (NDD+ / EP−; n = 54), and in subjects with negative NDD results (NDD−; n = 34). Compared to the NDD− controls (379.8 ± 125.2 pg/mL), NDD+ patients showed, on average, highly significantly increased CSF αSyn (519 ± 141.3 pg/mL, p < 0.01), but without differences between NDD+ / EP+ and NDD+ / EP− subgroups (p = 0. 38). Moderate but highly significant association was observed between concentrations of αSyn and Tau (r = 0.47, p < 0.01) and pTau181 (r = 0.65, p < 0.01). Adjusted for diagnoses, age, and sex, subjects with more advanced neurodegeneration on neuroimaging showed significantly lower αSyn concentrations (p < 0.02). In the setting AD versus controls, the area under the receiver operating characteristic (ROC) curve was 0.804 [0.712; 0.896] with the sensitivity and the specificity of 0.863 and 0.618, respectively. αSyn in AD patients does not differentiate between subjects with- and without EP. Its increased average concentration reflects probably neurodegenerative process, and is not specific for any pathophysiologic mechanisms. Further studies are necessary to explain the role of CSF αSyn as a potential biomarker.

scholarly journals Cerebrospinal Fluid Hypocretin and Nightmares in Dementia Syndromes

2021 ◽  
pp. 19-25
Author(s):  
Lynn Marie Trotti ◽  
Donald L. Bliwise ◽  
Glenda L. Keating ◽  
David B. Rye ◽  
William T. Hu
Keyword(s):  
Cerebrospinal Fluid ◽  
Alzheimer Disease ◽  
Cholinesterase Inhibitor ◽  
Dementia With Lewy Bodies ◽  
Lewy Bodies ◽  
Cognitively Normal ◽  
Dementia Patients ◽  
Sleep Questionnaires ◽  
Sleep Alterations ◽  
Normal Controls

Background/Aims: Hypocretin promotes wakefulness and modulates REM sleep. Alterations in the hypocretin system are increasingly implicated in dementia. We evaluated relationships among hypocretin, dementia biomarkers, and sleep symptoms in elderly participants, most of whom had dementia. Methods: One-hundred twenty-six adults (mean age 66.2 ± 8.4 years) were recruited from the Emory Cognitive Clinic. Diagnoses were Alzheimer disease (AD; n = 60), frontotemporal dementia (FTD; n = 21), and dementia with Lewy bodies (DLB; n = 20). We also included cognitively normal controls (n = 25). Participants and/or caregivers completed sleep questionnaires and lumbar puncture was performed for cerebrospinal fluid (CSF) assessments. Results: Except for sleepiness (worst in DLB) and nocturia (worse in DLB and FTD) sleep symptoms did not differ by diagnosis. CSF hypocretin concentrations were available for 87 participants and normal in 70, intermediate in 16, and low in 1. Hypocretin levels did not differ by diagnosis. Hypocretin levels correlated with CSF total τ levels only in men (r = 0.34; p = 0.02). Lower hypocretin levels were related to frequency of nightmares (203.9 ± 29.8 pg/mL in those with frequent nightmares vs. 240.4 ± 46.1 pg/mL in those without; p = 0.05) and vivid dreams (209.1 ± 28.3 vs. 239.5 ± 47.8 pg/mL; p = 0.014). Cholinesterase inhibitor use was not associated with nightmares or vivid dreaming. Conclusion: Hypocretin levels did not distinguish between dementia syndromes. Disturbing dreams in dementia patients may be related to lower hypocretin concentrations in CSF.

Sign in / Sign up

Export Citation Format

Share Document