Burak Önal

The interleukin 1 alpha, interleukin 1 beta, interleukin 6 and alpha-2-macroglobulin serum levels in patients with early or late onset Alzheimer's disease, mild cognitive impairment or Parkinson's disease

Alzheimers disease (EOAD, LOAD), mild cognitive impairment (MCI), Parkinsons disease (PD) and healthy controls were included to determine the serum interleukin-1s (IL-1α, IL-1β), IL-6 and alpha-2-macroglobulin (α2M) levels using ELISA. IL-6 might be a significant contributor to the inflammatory response in LOAD. The MCI data indicate that IL-1s, α2M and BDNF are somehow related, and this relationship might allow MCI patients to be more similar to the healthy controls. A correlation analysis of multiple biomarkers in different neurodegenerative disorders might be more useful than determining the levels of a single cytokine in a single disorder.

BDNF, TNFα, HSP90, CFH, and IL-10 Serum Levels in Patients with Early or Late Onset Alzheimer's Disease or Mild Cognitive Impairment

Identifying early-detection biomarkers have become an increasingly important approach in the treatment and prevention of Alzheimers disease (AD). In this study, we investigated the potential of brain-derived neurotrophic factor (BDNF), complement factor H (CFH), tumor necrosis factor-α (TNFα), interleukin 10 (IL-10), and heat shock protein 90 (Hsp90) as serum biomarkers for AD in a cohort of the Turkish population because they have been suggested to be associated with AD. Serum BDNF, CFH, TNFα, IL-10, and Hsp90 levels in three groups of patients, early-onset AD (EOAD; age of onset < 65; n = 22), late-onset AD (LOAD; age of onset > 65; n = 54), and mild cognitive impairment (MCI) (n = 30), were compared with age-matched healthy controls (age < 65, n = 18 and age > 65; n = 32) using ELISA. The serum BDNF levels significantly decreased and TNFα levels significantly increased in the EOAD and LOAD groups compared to the age-matched healthy controls. There was a correlation between serum TNFα and IL-10 levels in the LOAD and healthy control groups. Serum CFH levels in the LOAD and MCI patients were significantly decreased compared with controls. Serum Hsp90 levels in the EOAD, LOAD, and MCI patients were significantly decreased compared with controls. The protein misfolding, the inflammatory response, and decreased neurotrophic factor synthesis are all suggested to be related to AD type brain pathology, and our results indicate these alterations might be traced from serum samples. For accurate early diagnosis of AD, it is important to determine a profile of alterations in multiple biomarkers in large-scale population studies.

Vitamin D deficiency might pose a greater risk for ApoEɛ4 non-carrier Alzheimer’s disease patients

Vitamin D is a secosteroid hormone that shares a synthetic pathway with cholesterol. ApoE, which is involved in the transport of cholesterol, is the most significant genetic risk factor for sporadic Alzheimer’s disease (AD). Surprisingly, recent studies have indicated the presence of an evolutionary juncture between these two molecules. To demonstrate this possible relationship, we investigated serum levels of 25-hydroxyvitamin-D3 (25OHD) in patients with early onset-AD (EOAD; n:22), late onset-AD (LOAD; n:72), mild cognitive impairment (MCI; n:32) and in healthy subjects (n:70). We then analyzed the correlation between 25OHD and cytokines, BDNF and Hsp90 with respect to ApoE alleles, as these molecules were investigated in our previous studies. The LOAD patients had low levels of 25OHD, but these low levels originated only from ApoEɛ4 non-carrier patients. Negative correlations were observed between serum 25OHD and TNFα, IL-1β or IL-6 levels in healthy subjects or MCI patients, but these same correlations were positive in LOAD patients. ApoE alleles indicated that these positive correlations exist only in ɛ4 carrier LOAD patients. Consequently, our results indicate that vitamin D deficiency presents a greater risk for ApoEɛ4 non-carrier AD patients than for ɛ4 carriers. Therefore, it might be beneficial to monitor the vitamin D status of ApoEɛ4 allele non-carrier AD patients.

Investigation of MTHFR gene C677T polymorphism in cardiac syndrome X patients

Definition of Cardiac Syndrome X (CSX) refers to groups of patients with positive exercise stress test and normal epicardial coronary arteries on coronary angiography accompanied by chest pain. Although the etiology of CSX is not completely understood, there is a common consensus that its pathophysiology may be associated with endothelial dysfunction resulting in impaired coronary flow. Some polymorphisms observed on the MTHFR gene cause inactivation of the MTHFR enzyme, leading to hyperhomocysteinemia and homocysteinuria, which are prominent risk factors of cardiovascular and cerebrovascular diseases. It was aimed to explain the association of the endothelial dysfunction, which is thought to play a role in the pathophysiology of CSX, with C677T polymorphism on MTHFR gene based on genetic basis.

Plasma Betatrophin Levels of Subjects Classified with Normal, Impaired, and Diabetic Glucose Tolerance, and Subjects with Impaired Fasting Glucose

This study was aimed to investigate whether betatrophin shows glucose intolerance or not. To access the plasma betatrophin levels after basal and glucose load, groups were classified as normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and diabetic glucose tolerance (DGT) according to WHO 2012 criteria. An oral glucose tolerance test was performed on age-matched subjects (n=220) with a body mass index (BMI)<27 kg/m2. Subjects were categorized as normoglycemic (n=55), IFG (n=50), IGT (n=60), and DM (n=55) according to the WHO criteria. Baseline betatrophin levels in DGT are significantly higher than in NGT (p<0.005), IFG (p<0.004), and IGT (p<0.001). Male subjects have significantly higher betatrophin levels than female subjects (p<0.01). In DGT, betatrophin of male subjects was found to be significantly higher than the betatrophin of male subjects in NGT (p<0.04), IFG (p<0.01), and IGT (p<0.01). Significant relationship between betatrophin and both ages and HbA1c in all groups were observed. When ages were accepted as an independent factor, significant correlation between betatrophin and ages were found. Betatrophin is increased and associated with age and HbA1c in DGT. Males had higher betatrophin levels compared with females in DGT group. As no obvious betatrophin deficiency to substitute in IFG and IGT individuals were observed, betatrophin levels appeared to be related to the pathogenesis of the diabetic stages rather than prediabetic stages.

Does Inflammation Have a Role in the Pathogenesis of Cardiac Syndrome X? A Genetic-Based Clinical Study With Assessment of Multiple Cytokine Levels

We compared Turkish patients with cardiac syndrome X (CSX) and controls with respect to serum pro- and anti-inflammatory cytokine levels, as well as the single-nucleotide polymorphisms located in the promoter regions of their related genes. This study included 111 consecutive patients angiographically diagnosed with CSX and 111 healthy controls with similar demographic characteristics. Serum interleukin (IL) 6, tumor necrosis factor α (TNF-α), and IL-10 levels were measured, and the genotypes of the patients and controls were determined using standard methods. Serum IL-6 and IL-10 levels were significantly higher in the CSX group than in the control group (P < .01, respectively). Serum TNF-α level was lower in the CSX group than in the control group (P < .001). On the other hand, participants with CSX and healthy controls were not significantly different with respect to the genotype distributions of IL-6, TNF-α, and IL-10 genes. As a result of our study, both pro-inflammatory and anti-inflammatory cytokines may play a role in the pathogenesis of CSX. In contrast, the studied gene polymorphisms did not influence CSX pathogenesis.

Serum interleukin 1 alpha and alpha 2 macroglobulin levels in patients with early- or late-onset Alzheimer’s disease or mild cognitive impairment

aim of the current study was to compare levels of trace element Cu (free copper and ceruloplasmin bound) in the serum of AD patients (n1⁄444) and matched controls (n1⁄452). The objectives also included assessing their relationship with cognitive and behavioural and psychological functioning associated with dementia. Tools used were Clinical Dementia Rating (CDR), Hindi Mental Status Examination (HMSE), Everyday Abilities scale for Indians (EASI) and Neuropsychiatric Inventory (NPI) Results: Gender distribution among AD group was 45% males and 55% females and in HC group 52% males and 48% females. Mean age at assessment for AD group was 68.32 69.74 years and for HC group was 65.75 67.6 years. No significant difference was found between the two groups on age and gender. AD group obtained a lower mean score as compared to the HC group on HMSE, and higher on CDR, EASI & NPI indicating a poorer performance by AD group. AD group was found to have lower levels of total serum copper level (102.2 6 23.6 ug/dl) as compared to the control group (115.9627.9 ug/dl). Also, Serum free copper level was found to be lower in AD group (34.1611.2 ug/dl) as compared to HC group (46.1614.8 ug/dl). No significant difference was found between the two groups on Serum ceruloplasmin levels Both total and free copper (but not ceruloplasmin per se) were found to be lesser (p1⁄40.01 and p<0.001 respectively) in cases than in controls. Conclusions:No appreciable difference could be noted in levels of serum ceruloplasmin between the AD and healthy control groups. However, significant decrease observedwith copper levels in the AD may account, in part, for decreased copper-dependent biochemical activities such as cytochrome c oxidase required for energy generation and superoxide dismutase (free radical scavenging enzyme) described in AD.

Compromised regulation of serum cytokine levels and BDNF due to low levels of vitamin d in patients with early- or late-onset Alzheimer’s disease or parkinson’s disease

ASSOCIATIONS BETWEEN BDNF SERUM LEVELS AND ALZHEIMER’S DISEASE-RELATED MEASURES: THE FRAMINGHAM STUDY Galit Weinstein, Sarah R. Preis, Alexa S. Beiser, Claudia L. Satizabal, Nicole L. Spartano, Tai C. Chen, Vasan S. Ramachandran, Sudha Seshadri, University of Haifa, Haifa, Israel; Boston University School of Public Health, Boston, MA, USA; The Framingham Study, Framingham, MA, USA; Boston University School of Medicine, Boston, MA, USA; The Framingham Heart Study, Framingham, MA, USA. Contact e-mail: galitwai@bu.edu