title: Evaluation of selenium, redox status and their association with plasma amyloid/tau in Alzheimer's disease.
abstract: The aim of the study was to evaluate blood selenium and antioxidants as possible oxidative stress markers in Alzheimer's disease (AD) along with amyloid β42 (Aβ42) and tau by comparing them with vascular dementia (VD) and age-matched healthy controls. Selenium, total tau, Aβ42, glutathione (GSH) and malondialdehyde (MDA) levels and the activities of antioxidant enzymes were analysed in the blood of AD patients (n = 30), VD patients (n = 35) and controls (n = 40) from South India. Plasma Aβ42 level was significantly higher (P < 0.001) in both AD and VD compared to controls. Total tau and tau-to-amyloid ratio were significantly lower in both AD and VD (P < 0.001), compared to controls, and a significant difference (P < 0.01 and P < 0.05, respectively) was also observed between AD and VD. The receiver operating characteristic (ROC) curve-derived cutoff values of <3.5 for tau-to-Aβ42 ratio and <520 pg/ml for total tau showed sensitivity and specificity of around 67-72 % for differentiating AD from VD and around 90 % for AD from controls, indicating that they could serve as reliable AD-specific markers. The MDA levels were significantly higher (P < 0.001) in both dementia groups along with a significant decrease (P < 0.001) in reduced GSH levels, indicating elevated oxidative stress and altered redox status in both forms of dementia. Selenium levels did not vary significantly between the three groups. The activity of glutathione peroxidase increased in both AD and VD compared to controls, with a concomitant decrease in glutathione reductase and glucose-6-phospate dehydrogenase (P < 0.001) activity. The activity of thioredoxin reductase was significantly lower in both patient groups (P < 0.001) compared to healthy controls. No correlation was observed between selenium and activities of selenoenzymes, tau, Aβ42 or tau-to-Aβ42 ratio, when analysing independently, indicating that blood selenium may not be directly involved in Aβ production and in regulating tau/Aβ42-mediated mechanism in AD. The present study emphasizes the enhanced oxidative stress in AD pathology and plasma tau and tau-to-amyloid ratio as possible markers to differentiate AD from VD. The study also points that blood selenium may not be involved in regulating oxidative stress in AD, and a longitudinal study correlating plasma and cerebrospinal fluid (CSF) selenium and selenoprotein levels is warranted.
authors.affiliation: Department of Biotechnology, PSG College of Technology, Peelamedu, Coimbatore, Tamil Nadu, 641004, India.
authors.forename: Sreeram
authors.initials: S
authors.lastname: Krishnan
authors.forename: P
authors.initials: P
authors.lastname: Rani
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000097:blood* / Q000175:diagnosis; D016229:Amyloid beta-Peptides / Q000097:blood*; D000975:Antioxidants / Q000032:analysis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010446:Peptide Fragments / Q000097:blood*; D012643:Selenium / Q000097:blood*; D016875:tau Proteins / Q000097:blood*
chemical_list: D016229:Amyloid beta-Peptides; D000975:Antioxidants; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D012643:Selenium