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Oxidative stress plays a pivotal and early role in the pathophysiology of Alzheimer's disease (AD). There is convincing evidence that oxidative alterations in AD and in mild cognitive impairment (MCI) patients are not limited to the brain but are extended to the blood compartment. However, the oxidative pattern in plasma is still inconclusive. Moreover, their potential association with the clinical scores MMSE (Mini-Mental State Examination) and MoCA (Montreal Cognitive Assessment) is poorly investigated. The aim of our study was to establish a pattern of blood-based redox alterations in prodromal AD and their evolution during the progression of the disease. Our results showed a reduction in the total antioxidant capacity (TAC) and an increase of the stress-response proteins apolipoprotein J (ApoJ) and Klotho in MCI subjects. For the first time, we evidenced circulating-proteasome activity. We found that the alteration of the circulating-proteasome activity is associated with the accumulation of oxidized proteins in plasma form early AD. Interestingly, the TAC, the levels of vitamin D and the activity of proteasome were positively associated to the clinical scores MMSE and MoCA. The levels of protein carbonyls and of ApoJ were negatively associated to the MMSE and MoCA scores. The levels of apolipoprotein D (ApoD) were not different between groups. Interestingly, the receiver operating characteristic (ROC) curves analysis indicated that these redox markers provide a fair classification of different groups with high accuracy. Overall, our results strengthen the notion that some specific oxidative markers could be considered as non-invasive blood-based biomarkers for an early MCI diagnosis and AD progression., (Copyright © 2018. Published by Elsevier Inc.)

Objectives: Progressive degenerative syndromes which affect brain, altering memory, behavior, cognition and emotion, are commonly defined as dementia. It was suggested that serum human kallikrein 6 (KLK6), clusterin (CLU) and adiponectin (ADPN) in combination with inflammation markers, neuroimaging and neuropsychological testing could assist in discriminating dementia patients from control individuals. Our aim was therefore to compare serum concentrations of KLK6, CLU and ADPN and inflammatory marker, interleukin-6 (IL-6), in patients suffering from Alzheimer's disease (AD), patients with vascular dementia (VAD), cognitively healthy participants (CHP) and those with mild cognitive impairment (MCI)., Design and Methods: Serum samples were collected from AD, VAD and MCI patients admitted to the University Department of Neurology (Zagreb, Croatia) for regular follow-up. All patients underwent standard neuroimaging procedures including brain CT, neurosonological assessment with intima-media thickness (IMT) and breath holding index (BHI) calculations. Cognitive abilities were tested using standard Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Concentrations of KLK6, CLU, ADPN and IL-6 were determined in all serum samples., Results: We have recruited a total of 235 participants, divided in 4 groups: AD (N=70), VAD (N=67), MCI (N=48) and CHP (N=50). Serum concentrations of KLK6 (P=0.137), CLU (P=0.178) and ADPN (P=0.268) did not differ between AD, VAD, MCI and cognitively healthy control group of participants, whereas IL-6 was significantly higher in VAD patients than in AD, MCI and CHP individuals (P=0.014). There was no association between investigated biomarkers and clinical patient parameters., Conclusions: Serum concentrations of KLK6, CLU and ADPN do not differ between AD, VAD and controls with and without mild cognitive impairment. Higher IL-6 levels in VAD group point to the inflammatory component in the development of vascular dementia. Investigated biomarkers are not associated with neuroimaging findings and neuropsychological patient data., (Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Clusterin is a multifunctional chaperone protein that has repeatedly been linked to Alzheimer's disease (AD) pathogenesis and, more recently, also to Parkinson's disease (PD) by both genetic and proteomic analyses. Although clusterin is detectable in cerebrospinal fluid (CSF) and plasma, studies comparing clusterin levels in PD patients and controls have been scarce and yielded conflicting data. The aim of the present study was to determine whether CSF and/or plasma clusterin levels differ between PD patients and controls and are related to disease severity. We measured CSF and plasma clusterin levels in a group of 52 PD patients and in 50 age-matched neurologically healthy controls and found that clusterin levels in CSF and plasma were not different between the two groups. Furthermore, clusterin levels in CSF and plasma were not associated with disease duration, stage or severity. CSF clusterin levels did, however, correlate with CSF levels of total tau, phospho-tau and amyloid-β-42. We elaborate on the identified correlations between levels of clusterin and AD related proteins and on possible explanations for the discrepant findings in clusterin studies in PD so far., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Hepatocellular carcinoma (HCC) is an increasing problem in Egypt. Clusterin has been reported to play a significant role in tumorigenesis., Aim: The aim of this study is to evaluate clusterin as a marker for evaluating diagnosis and metastasis potential of viral-related HCC., Methods: Eighty patients with HCC, 30 patients with liver cirrhosis, 30 patients with chronic hepatitis and 30 healthy controls were enrolled in study. Estimation of serum clusterin was done by enzyme linked immunosorbent assay., Results: Serum clusterin levels were significantly increased in patients with HCC. Serum clusterin was highly increased in patients with poorly differentiated tumor, capsular infiltration, portal vein invasion and lymph node infiltration. Receiver operator characteristic curve showed that clusterin had a greater area under curve value (0.95) than that of alpha fetoprotein (0.85). At cutoff value of 128 μg/mL, serum clusterin yielded (90%) sensitivity and (87%) specificity for predicting HCC., Conclusion: We concluded that clusterin is a promising useful marker for diagnosis of HCC. Clusterin might be deemed as a useful marker for predicting the progression and metastasis potential of HCC., (Copyright © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Objectives: To assess whether the serum level of clusterin and its density could be used as novel biomarkers of prostate cancer., Methods: Sera were obtained from 380 patients with prostate cancer and 120 with benign prostatic hyperplasia. Serum clusterin level was measured by a sandwich enzyme immunoassay, and clusterin density, which was determined by dividing the serum clusterin level by the prostate volume, was also calculated. These findings were analyzed with respect to several clinicopathologic factors., Results: The mean serum level of clusterin in prostate cancer patients was significantly higher than that in the benign prostatic hyperplasia group. Both the serum clusterin level and clusterin density in prostate cancer patients were significantly associated with major prognostic factors other than biopsy Gleason score. Of the 380 prostate cancer patients, 162 underwent radical prostatectomy and pelvic lymphadenectomy, and 104 and 58 were diagnosed as having organ-confined and extraprostatic diseases, respectively. The clusterin density in patients with organ-confined disease was significantly higher than that in patients with extraprostatic disease; however, there was no significant difference in the serum clusterin level between these 2 groups. Furthermore, biochemical recurrence-free survival in patients with elevated clusterin density was significantly lower than that in patients with normal density., Conclusions: These findings suggest that serum clusterin level and its density could serve as a useful practical adjuncts to conventional parameters for estimating the extension of prostate cancer., (2010 Elsevier Inc. All rights reserved.)

Paraoxonase 1 (PON1) associates to specific high-density lipoproteins (HDLs)--those containing apolipoprotein A-I (apoA-I) and apolipoprotein J (apoJ)--and is largely responsible for their antiatherogenic properties. Caloric restriction (CR) has been shown to reduce major atherosclerotic risk factors. The aims of this work were to study PON1 activity response to CR (40% over 14 weeks) and to elucidate whether there are adaptive differences related to gender. Serum and liver paraoxonase and arylesterase activities, serum triglyceride, total and HDL cholesterol concentrations, serum PON1, apoA-I and apoJ contents and liver PON1 mRNA levels were measured. No effects of CR or gender were observed in triglyceride, total cholesterol concentration and PON1 mRNA levels. HDL cholesterol was higher in female rats than in male rats and increased with CR only in the latter animals. Serum PON1 activities tended to be higher in female rats and dropped with CR, with females showing the biggest decrease. Serum PON1 content was higher in female rats and decreased in both genders with CR, whereas apoA-I and apoJ contents, which were higher in female rats too, decreased only in the former animals, accounting for the high PON1 activity decrease observed in these animals. In conclusion, the short-term CR-associated reduction of serum PON1 activity and PON1, apoA-I and apoJ levels points toward a reduced stability of HDL-PON1 complexes and/or HDL particle levels responsible for PON1 transport and function in the blood. Moreover, the variations in PON1 activity and apolipoprotein levels show gender-related differences that are indicative of a different adaptive strategy of male and female rats when faced with a period of food restriction.