Plasmatic apelin shows a promising potential as a screening biomarker for atrial fibrillation.

OBJECTIVES: Purpose of this study was to evaluate properties of apelin, a peptide detectable in peripheral blood, for atrial fibrillation (AF) detection in a diverse population of patients covering a broad spectrum from healthy to polymorbid patients. BACKGROUND: AF is the most common cardiac arrhythmia with constantly increasing incidence and prevalence. Currently available diagnostic tools do not provide sufficient detection rate. Large proportion of patients with AF remains undiagnosed and the possibility of screening at-risk groups would be significantly beneficial. METHODS: We designed this study as a multi-centre retrospective study. Study population included 183 patients. 64 in non-AF and 119 in AF group. RESULTS: Apelin plasma concentration was significantly lower in AF group compared to non-AF group (p < 0.001). Receiver operating characteristic analysis of apelin as a predictor of AF scored area under the curve of 0.79, sensitivity = 0.941 and specificity = 0.578. Multivariate analysis using logistic regression adjusted for age, BMI, apelin, dilated LV, dilated LA, arterial hypertension, and gender showed only apelin and age to be statistically significant contributors for AF. CONCLUSION: Apelin might be a promising biomarker for detecting AF in our study population. These results suggest promising potential of apelin as a screening biomarker for AF (Tab. 2, Fig. 1, Ref. 46). Text in PDF www.elis.sk Keywords: biomarker, apelin, arrhythmia, atrial fibrillation.

Cerebrospinal fluid markers analysis in the differential diagnosis of dementia with Lewy bodies and Parkinson's disease dementia.

Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) share a couple of clinical similarities that is often a source of diagnostic pitfalls. We evaluated the discriminatory potential of brain-derived CSF markers [tau, p-tau (181P), Aß1-42, NSE and S100B] across the spectrum of Lewy body disorders and assessed whether particular markers are associated with cognitive status in investigated patients. The tau CSF level, amyloid ß1-42 and p-tau/tau ratio were helpful in the distinction between DLB and PDD (p = 0.04, p = 0.002 and p = 0.02, respectively) as well as from PD patients (p < 0.001, p = 0.001 and p = 0.002, respectively). Furthermore, the p-tau/tau ratio enabled the differentiation of DLB with mild dementia from PDD patients (p = 0.02). The CSF tau and p-tau levels in DLB and CSF tau and p-tau/tau ratio in PDD patients reflected the severity of dementia. Rapid disease course was associated with the decrease of Aß1-42 in DLB but not in PDD. Elevation of S100B in DLB (p < 0.0001) as well as in PDD patients (p = 0.002) in comparison to controls was estimated. Hence, with the appropriate clinical context; the CSF marker profile could be helpful in distinguishing DLB from PDD patients even in early stages of dementia.

Association of CD33 rs3865444:C˃A polymorphism with a reduced risk of late-onset Alzheimer's disease in Slovaks is limited to subjects carrying the APOE ε4 allele.

CD33 rs3865444:C>A single nucleotide polymorphism (SNP) has been previously associated with the risk of late-onset Alzheimer's disease (LOAD); however, the results have been inconsistent across different populations. CD33 is a transmembrane receptor that plays an important role in AD pathogenesis by inhibiting amyloid ß42 uptake by microglial cells. In this study, we aimed to validate the association between rs3865444 and LOAD risk in the Slovak population and to evaluate whether it was affected by the carrier status of the major LOAD risk allele apolipoprotein (APOE) ε4. CD33 rs3865444 and APOE variants were genotyped in 206 LOAD patients and 487 control subjects using the polymerase chain reaction-restriction fragment length polymorphism method and direct sequencing, respectively. Logistic regression analysis revealed a significant association of rs3865444 A allele with a reduced LOAD risk that was only present in APOE ε4 allele carriers (AA + CA versus CC: p = .0085; OR = 0.45; 95% CI = 0.25-0.82). On the other hand, no such association was found in subjects without the APOE ε4 (p = .75; OR = 0.93; 95% CI = 0.61-1.42). Moreover, regression analysis detected a significant interaction between CD33 rs3865444 A and APOE ε4 alleles (p = .021 for APOE ε4 allele dosage and p = .051 for APOE ε4 carriage status), with synergy factor (SF) value of 0.49 indicating an antagonistic effect between the two alleles in LOAD risk. In conclusion, our results suggest that CD33 rs3865444:C˃A substitution may reduce the risk of LOAD in Slovaks by antagonizing the effect conferred by the major susceptibility allele APOE ε4.

HMGB1 as a potential new marker of disease activity in patients with multiple sclerosis.

OBJECTIVES: Neuroinflammation represents one of the two major pathological components of multiple sclerosis (MS). The aim of our study was to find the role of the late pro-inflammatory cytokine HMGB1 (high mobility group box) in MS pathogenesis. SUBJECTS AND METHODS: A total of 165 patients from three MS centers in Slovakia were enrolled in the study. Patients underwent a complex clinical investigation and their plasma levels of HMGB1 were analyzed by a sandwich ELISA test. RESULTS: MS patients had 4.5 times higher plasma level of HMGB1 (median, 13.529 ng/mL; IQR = 2.330-113.45) than healthy controls (median, 2.999 ng/mL; IQR = 1.686-9.844; P < 0.0001). The concentrations of HMGB1 were significantly associated with increased number of affected areas diagnosed by MRI (P < 0.0001) (the median for one affected area, 4.205 ng/mL; median for five affected areas, 17.843 ng/mL; P < 0.05). Patients with at least one active lesion in any of the affected areas in the brain had significantly higher plasma levels of HMGB1 (median, 20.118 ng/mL; IQR, 3.693-100.12) than those without any active lesion (median, 16.695 ng/mL; IQR, 3.255-113.45; P < 0.0235). We found also a very highly significant association of HMGB1 plasma levels with clinical condition expressed as EDSS (expanded disability status scale) (P < 0.0001); patients with higher EDSS had higher levels of HMGB1 (EDSS ≤ 2.5, 11.648 ng/mL vs. EDSS ≥ 3, 17.549 ng/mL; P = 0.0115). CONCLUSION: Our results suggest chronic low-grade inflammation in MS patients that correlates with clinical conditions of MS patients, and for HMGB1 as a possible target molecule in future therapy.

Tacrolimus-induced parkinsonism in a patient after liver transplantation - case report.

BACKGROUND: Hepatic encephalopathy may manifest by a wide spectrum of neuropsychiatric symptoms, including cognitive impairment, seizures or extrapyramidal symptoms. The liver transplant can lead to improvement of the signs of encephalopathy but subsequent immunosuppressive treatment might possess pronounced neurotoxicity. CASE PRESENTATION: We present a case report of a patient with chronic liver disease who developed signs of Parkinsonism after an orthotopic liver transplant, with consecutive immunosuppressant treatment with tacrolimus. Despite the improvement of liver functions due to the cytostatic treatment, a progressive worsening of neuropsychiatric symptoms associated with the presence of tremor was observed. Metabolic as well as endocrine dysfunctions were excluded as the primary causes of this condition. A brain CT did not reveal structural pathology. Signs of severe, symmetric Parkinsonism - with resting tremor, bradykinesia, rigidity and severe postural instability were observed. A brain MRI was performed with the presence of T2- hyperintensities in basal ganglia bilaterally. Tacrolimus blood concentration was elevated; hence the dose was reduced and later switched to less toxic sirolimus. Subsequently, clinical signs markedly improved after treatment modification. Improvement of clinical symptomatology after tacrolimus discontinuation supports the drug-induced etiology of this neurological condition. CONCLUSIONS: Cytostatic treatment after solid organ transplantation often leads to signs of encephalopathy. If necessary, the dose of cytostatics needs to be reduced, or a less toxic agent must be chosen for the therapy. This modification is usually efficient with no further need for neurological intervention.

TNFRSF1A polymorphisms and their role in multiple sclerosis susceptibility and severity in the Slovak population.

Tumour necrosis factor (TNF)-mediated signalling plays a key role in inflammatory and neurodegenerative processes leading to the development of multiple sclerosis (MS). Recent studies have highlighted the role of tumour necrosis factor receptor superfamily member 1A (TNFRSF1A) gene encoding the type 1 TNF receptor in the genetic predisposition to MS. This study aimed to validate the association of TNFRSF1A rs1800693 and rs4149584 polymorphisms with susceptibility to MS in the Slovak population and analyse their influence on age at disease onset, severity, and disability progression. Polymerase chain reaction-restriction fragment length polymorphism method was used to genotype both TNFRSF1A polymorphisms in 541 MS patients and 724 healthy controls. Logistic regression analysis revealed a significantly increased risk of developing MS for the carriers of rs1800693 C allele (TC + CC vs. TT: pcorr = 0.005; OR = 1.61; 95% CI = 1.23-2.12), irrespective of sex and carriage of the major MS risk allele HLA-DRB1*15:01. On the other hand, no association could be found between rs4149584 and MS risk (GA + AA vs. GG: pcorr = 1.00; OR = 1.25; 95% CI = 0.71-2.21). Moreover, neither polymorphism was significantly associated with age at disease onset, MS Severity Score (MSSS) or MS Progression Index (PI) in any of the inheritance models. In conclusion, our results provide support for a sex- and HLA-DRB1*15:01-independent association of TNFRSF1A rs1800693 SNP with MS susceptibility, but not with age at disease onset, severity or rate of disability accumulation.

A Novel Association of Polymorphism in the ITGA4 Gene Encoding the VLA-4 α4 Subunit with Increased Risk of Alzheimer's Disease.

Alzheimer's disease (AD) is the most prevalent cause of dementia in elderly people worldwide. Many studies support the hypothesis that the inflammation of the CNS contributes to the neurodegeneration and disease progression. The integrin molecule α4ß1, also known as very late antigen 4 (VLA-4), belongs to adhesion molecules that activate the inflammatory process through the migration of immune cells into the CNS. Therefore, the objective of our study was to analyze the association between two polymorphisms located in the ITGA4 gene encoding the α4 subunit of VLA-4 and the risk of AD. 104 late-onset AD patients and 206 control subjects from Slovakia were genotyped for ITGA4 gene SNP polymorphism rs113276800 (-269C/A) and rs1143676 (+3061A/G). The same study cohorts were also genotyped for the APOE-ε4, which is a known genetic factor associated with increased risk of AD developing. ITGA4 polymorphism analysis revealed significantly higher frequency of the +3061AG carriers in AD group compared to the controls (P ≤ 0.05). Following the APOE-ε4 stratification of study groups, the association remained significant only in APOE-ε4 noncarriers. Our study suggests a novel association of ITGA4 +3061A/G polymorphism with AD and its possible contribution to the disease pathology.

Adiponectin Gene Polymorphisms: A Case-Control Study on Their Role in Late-Onset Alzheimer's Disease Risk.

Adiponectin, a hormone secreted by adipose tissue, plays a complex role in regulating metabolic homeostasis and has also garnered attention for its potential involvement in the pathogenesis of late-onset Alzheimer's disease (LOAD). The objective of this study was to investigate the association of ADIPOQ variants with plasma adiponectin levels and LOAD risk in subjects from the Slovak Caucasian population. For this purpose, 385 LOAD patients and 533 controls without cognitive impairment were recruited and genotyped for a total of eighteen ADIPOQ single nucleotide polymorphisms (SNPs). Both single-locus and haplotype-based logistic regression analyses were employed to assess the association of SNPs with LOAD risk, while linear regression analysis was used to explore their influence on adiponectin levels in LOAD patients. ADIPOQ variants rs822395 and rs2036373 in intron 1 were found to significantly elevate total adiponectin levels after accounting for several potential confounders. Additional SNPs in the 5' region and intron 1 exhibited a non-significant trend of association with adiponectin. However, none of the ADIPOQ SNPs showed an association with LOAD risk, neither in the whole-group analysis nor in subgroup analyses after stratification for sex or the APOE ε4 allele, a well-established LOAD risk factor. In summary, while adiponectin has emerged as a potential contributor to the development of LOAD, this study did not unveil any significant involvement of its gene variants in susceptibility to the disease.

Case Report: Stroke-like migraine attacks after radiation therapy syndrome: a rare complication 26 years after cranial radiotherapy.

Stroke-like migraine attacks after radiation therapy (SMART) syndrome is a rare delayed complication of cranial radiotherapy, that may present decades after brain irradiation. Here we present a case of 41-year old patient with a history of grade 3 oligodendroglioma, epilepsy and migraine, 26 years after brain radiation therapy, who was admitted with right hemicranial headache, nausea, left homonymous hemianopsia, weakness of the left arm and left-sided hemihypesthesia. After considering alternate diagnoses, we ultimately diagnosed SMART syndrome. Despite its rare occurrence and unknown pathophysiology, there are more case reports of SMART syndrome reported due to advancements in oncology treatment and increasing patients' survival rates. Therefore, diagnosis of SMART syndrome should always be considered in patients with a history of cranial radiation presenting with focal neurologic deficits and migraine, especially with a change in pattern of their usual migraine attack.

Tolcapone improves outcomes in patients with Parkinson disease treated by levodopa/carbidopa intestinal gel: A pilot study.

BACKGROUND: Patients with Parkinson disease (PD) treated with levodopa/carbidopa intestinal gel (LCIG) have higher prevalence of hyperhomocysteinemia and peripheral nerves damage. OBJECTIVE: The aim of our study was to test the effect of catechol-O-methyl transferase inhibitor tolcapone-as an add-on therapy to LCIG in patients with PD-on homocysteine (HCY) metabolism and nerve conduction study (NCS) parameters. METHODS: We evaluated NCS and serum B12, folic acid, and homocysteine in 16 patients with advanced PD on LCIG. Quality of life (QoL) was also assessed. Six subjects were treated with tolcapone add-on therapy (and LCIG dose reduction), 5 with B vitamin supplementation, and 5 without additional treatment. RESULTS: The level of HCY increased among patients without treatment (4.95 ± 12.54), and decreased in the vitamin (-17.73 ± 11.82) and tolcapone groups (-8.81 ± 8.36). Patients with tolcapone demonstrated improvement in polyneuropathic symptoms and signs compared with patients treated with vitamins or those without additional treatment (-0.83, d = 0.961). Although the most robust improvement in NCS parameters were observed with tolcapone, the findings were inconsistent to prove the effect of any intervention. Only tolcapone treatment was associated with improvement in QoL (d = 1.089). CONCLUSION: Our study indicates potential of tolcapone add-on therapy in LCIG treated patients in control of homocysteine levels, and improvement of polyneuropathic symptoms, as well as QoL.

Alzheimer's Disease Risk Variant rs3865444 in the CD33 Gene: A Possible Role in Susceptibility to Multiple Sclerosis.

Polymorphisms in genes encoding receptors that modulate the activity of microglia and macrophages are attractive candidates for participation in genetic susceptibility to multiple sclerosis (MS). The aims of the study were to (1) investigate the association between Alzheimer's disease-linked variant rs3865444:C>A in the CD33 gene and MS risk, (2) assess the effect of the strongest MS risk allele HLA-DRB1*15:01 on this association, and (3) analyze the correlation of rs3865444 with selected clinical phenotypes, i.e., age of onset and disease severity. CD33 rs3865444 was genotyped in a cohort of 579 patients and 1145 controls and its association with MS risk and clinical phenotypes was analyzed by logistic and linear regression analysis, respectively. Statistical evaluation revealed that rs3865444 reduces the risk of MS in the HLA-DRB1*15:01-positive subpopulation but not in the cohort negative for HLA-DRB1*15:01. A significant antagonistic epistasis between rs3865444 A and HLA-DRB1*15:01 alleles in the context of MS risk was detected by the interaction synergy factor analysis. Comparison of allele and genotype distribution between relapsing-remitting MS, secondary progressive MS, and control groups revealed that rs3865444 C to A substitution may also be associated with a decreased risk of transition of MS to its secondary progressive form, irrespective of the HLA-DRB1*15:01 carrier status. On the other hand, no correlation could be found between rs3865444 and the age of disease onset or MS severity score. Future studies are required to shed more light on the role of CD33 in MS pathogenesis.

Detection of Cerebrospinal Fluid Neurofilament Light Chain as a Marker for Alpha-Synucleinopathies.

Alpha-synucleinopathies, such as Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), are a class of neurodegenerative diseases. A diagnosis may be challenging because clinical symptoms partially overlap, and there is currently no reliable diagnostic test available. Therefore, we aimed to identify a suitable marker protein in cerebrospinal fluid (CSF) to distinguish either between different types of alpha-synucleinopathies or between alpha-synucleinopathies and controls. In this study, the regulation of different marker protein candidates, such as alpha-synuclein (a-Syn), neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and total tau (tau) in different types of alpha-synucleinopathies, had been analyzed by using an ultrasensitive test system called single-molecule array (SIMOA). Interestingly, we observed that CSF-NfL was significantly elevated in patients with DLB and MSA compared to patients with PD or control donors. To differentiate between groups, receiver operating characteristic (ROC) curve analysis resulted in a very good diagnostic accuracy as indicated by the area under the curve (AUC) values of 0.87-0.92 for CSF-NfL. Furthermore, we observed that GFAP and tau were slightly increased either in DLB or MSA, while a-Syn levels remained unregulated. Our study suggests NfL as a promising marker to discriminate between different types of alpha-synucleinopathies or between DLB/MSA and controls.

Wernicke encephalopathy-a rare complication of hyperemesis gravidarum.

We report a rare case of Wernicke encephalopathy (WE) in a 35-year-old woman with hyperemesis gravidarum (HG). Initially, the disease manifested as passivity, a loss of interest, sleeping too much, apathy and disorientation. The correct diagnosis was established after the detection of typical pathological findings of WE in the thalamus by magnetic resonance imaging (MRI), which was indicated for the appearance of eye symptomatology in the form of nystagmus. Subsequent treatment with thiamine led to rapid improvement in the patient's clinical status and a favorable course of pregnancy.

Chromogranin A Analysis in the Differential Diagnosis Across Lewy Body Disorders.

BACKGROUND: Chromogranin A (CgA) is a general marker of gut endocrine cells, which are part of the "gut-brain axis" in Parkinson's disease (PD). OBJECTIVE: We analyzed CgA as a marker of synaptic dysfunction to assess its role in the differential diagnosis across different Lewy body disorders. METHODS: We analyzed the CgA levels in the cerebrospinal fluid (CSF) and serum from 54 patients covering the spectrum of Lewy body disorders [13 Parkinson's disease (PD), 17 Parkinson's disease dementia (PDD), 24 dementia with Lewy bodies (DLB)] and 14 controls using an ELISA. RESULTS: A positive correlation was noted between CSF and serum CgA levels (ρ= 0.47, 95% CI: 0.24 to 0.65, p < 0.0001). The highest values of CgA in CSF and in serum were measured in DLB and there was a significant difference between DLB and PDD (p = 0.03 and p = 0.004). The serum levels of CgA in controls achieved lower values compared to DLB (p = 0.006). There was a gradual increase in serum levels from PD to PDD and DLB. An inverse correlation was seen between the CSF level of CgA and Aß42 (ρ  = -0.296, 95% CI: -0.51 to -0.04, p = 0.02). CONCLUSION: The incorporation of CgA analysis as an additional biomarker may be useful in the diagnostic work-up of Lewy body dementia. CgA analysis may be relevant in distinguishing DLB from PDD patients and presumably early stages of PD. Our data on altered serum levels in DLB pave the way to the development of blood-based parameters for the differential diagnosis, which however needs to be confirmed in a prospective study.

Cerebrospinal Fluid Total and Phosphorylated α-Synuclein in Patients with Creutzfeldt-Jakob Disease and Synucleinopathy.

High levels of total α-synuclein (t-α-synuclein) in the cerebrospinal fluid (CSF) were reported in sporadic Creutzfeldt-Jakob disease (sCJD). The potential use of t-α-synuclein in the discrimination of Lewy body dementias (i.e., Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB)) is still under investigation. In addition, phospho-serine-129 α-synuclein (p-α-synuclein) has been described to be slightly increased in the CSF of synucleinopathies. Here, we analyzed t-α-synuclein and p-α-synuclein concentrations and their ratio in the context of differential diagnosis of neurodegenerative diseases. We quantified the levels of CSF t-α-synuclein and p-α-synuclein in a cohort of samples composed of neurological controls (NC), sCJD, PDD, and DLB by means of newly developed specific enzyme-linked immunosorbent assays. T-α-synuclein and p-α-synuclein were specifically elevated in sCJD compared to other disease groups. The area under the curve (AUC) values for t-α-synuclein were higher for the discrimination of sCJD from dementias associated to Lewy bodies as compared to the use of p-α-synuclein. A combination of both markers even increased the diagnostic accuracy. An inverse correlation was observed in CSF between t-α-synuclein and p-α-synuclein, especially in the DLB group, indicating a disease-relevant association between both markers. In conclusion, our data confirm t-α-synuclein and p-α-synuclein as robust biomarkers for sCJD and indicate the potential use of colorimetric t-α-synuclein ELISAs for differential diagnosis of dementia types.

The phylogenesis and ontogenesis of the human pharyngeal region focused on the thymus, parathyroid, and thyroid glands.

The pharyngeal (branchial) region represents a classic example where the relationship between ontogenesis and phylogenesis has been demonstrated. It is a region where the development of gills during ontogenesis of all chordates has been recapitulated. In the process of evolution the pharyngeal region has undergone marked changes. While it functioned to ensure blood oxygenation and regulation of a constant internal environment in aquatic animals, it had to adapt to new and more complex functions in terrestrial vertebrates. The lungs have taken on the main role of blood oxygenation and the salivary glands now regulate ionic balance. The immune organs in mammals such as the thymus and the palatine tonsil, endocrine organs such as the parathyroid glands and the parafollicular cells of the thyroid gland, which produces calcitonin (originally as independent ultimobranchial bodies), as well as a part of the ear developed from the pharyngeal region. This article briefly summarizes the current knowledge regarding the phylogenesis and development of the human thymus, parathyroids, and the thyroid gland with a focus on the influence of neural crest cells during development.

Analysis of ICAM1 gene polymorphism in Slovak multiple sclerosis patients.

Infiltration of immune cells into CNS is one of the essential events in multiple sclerosis (MS) development. Adhesion molecules like the intercellular adhesion molecule 1 (ICAM-1) play critical role in this process. Therefore, the ICAM1 gene containing two important single-nucleotide polymorphisms (SNPs) belongs to candidate loci with possible involvement in MS susceptibility and/or severity. The objective of our case-control study was to analyze the association of two functional ICAM1 polymorphisms rs1799969 (or G241R) and rs5498 (or K469E) with susceptibility to MS and evaluate their influence on the age at disease onset, severity, neurological disability and progression rate. Two hundred forty-eight MS subjects (mean 39.2 years) and 208 age-matched controls (mean 35.6 years) were involved in the study. Genotyping of ICAM1 rs1799969 and rs5498 SNPs was performed by PCR-RFLP. Presence of the rs3135388 polymorphism tagging the major MS risk allele HLA-DRB1*15:01 allele was determined as well. Our analysis revealed no statistically significant association of ICAM1 polymorphisms with risk of MS development in the Slovak population. Stratification of study cohorts by gender, age at onset and presence of the HLA-DRB1*15:01 risk allele showed only moderate changes. Correlation of clinical findings as age at onset, Kurtzke Expanded Disability Status Scale, Multiple Sclerosis Severity Score and progression index with ICAM1 genotypes in MS patients revealed no significant association; however, patients with earlier onset of MS showed slightly higher frequencies of the homozygous G allele at rs5498 in comparison to other genotypes (P = 0.04), suggesting that GG carriers tend to induce MS at an earlier age.

Cerebrospinal α-synuclein in α-synuclein aggregation disorders: tau/α-synuclein ratio as potential biomarker for dementia with Lewy bodies.

Several studies have addressed the utility of cerebrospinal (CSF) α-synuclein levels as a potential biomarker of α-synuclein aggregation disorders. However, its relevance in the differential diagnostic context of neurodegenerative and movement disorders is still a contentious subject. Here, we report total CSF α-synuclein levels in a cohort of clinically diagnosed α-synuclein-related disorders encompassing Parkinson's disease, Parkinson's disease dementia, dementia with Lewy bodies and multiple system atrophy in comparison to essential tremor and neurological control cases. α-synuclein levels in α-synuclein-related disorders were significantly lower than in controls (p < 0.001). However, in the differential diagnostic context, only Parkinson's disease cases presented significant lower α-synuclein levels compared to essential tremor and neurological controls. In cases with clinically diagnosed α-synuclein pathology, CSF α-synuclein levels showed a moderate positive correlation with CSF tau and p-tau, but not with Aß42 levels. Due to elevated CSF tau levels in dementia with Lewy bodies samples, tau/α-synuclein ratio showed a good clinical accuracy in discriminating controls from dementia with Lewy bodies cases (AUC = 0.8776) compared to single α-synuclein (AUC = 0.7192) and tau (AUC = 0.7739) levels. In conclusion, α-synuclein alone lacks of clinical value as a biomarker of α-synuclein-related disorders, but in combination with total tau, it may improve the diagnosis of dementia with Lewy bodies.

Reduced plasma homocysteine levels in levodopa/entacapone treated Parkinson patients.

Hyperhomocysteinemia is not only a major risk factor for atherothrombotic disease, but is also strongly associated with an increased risk of dementia and cognitive impairment, both of which are common in the course of Parkinson's disease (PD). Previous work has found that levodopa increases plasma homocysteine concentrations. Animal studies have indicated that the catechol-O-methyltransferase (COMT) inhibitors can prevent levodopa-induced elevation of homocysteine concentrations by reducing the O-methylation of levodopa. The objective of our study was to assess the impact of entacapone, a COMT inhibitor, on plasma levels of homocysteine, serum folate, and vitamin B12 in levodopa-treated PD patients. Nineteen PD patients receiving only levodopa and 21 PD patients on a combination of levodopa and entacapone participated in the cross-sectional study. The control group consisted of 17 subjects on dopamine agonists. The mean plasma homocysteine concentration in the subjects on only levodopa was higher than that in the subjects on a combination of levodopa and entacapone (P=0.001) or in the control group (P=0.0001). Concentrations of serum vitamin B12 and serum folate were on average normal in all groups, but levodopa-treated subjects (with or without entacapone therapy) were more prone to have hypovitaminosis B12 (45%) than controls on dopamine agonists (6%). We suggest that the COMT inhibition may play a promising role in successfully controlling levodopa-induced hyperhomocysteinemia and in reducing the risk of pathologies probably linked to it. These preliminary findings and postulated hypotheses must now be confirmed in prospective studies.