title: Peripheral cytokines, C-X-C motif ligand10 and interleukin-13, are associated with Malaysian Alzheimer's disease.
abstract: OBJECTIVE
  Cytokines released from chronically-activated microglia could result in neuroinflammation. An accurate profile of the relationship between cytokines and Alzheimer's disease (AD) pathogenesis, as well as the patterns of these inflammatory mediators in AD patients could lead to the identification of peripheral markers for the disease. The present study was undertaken to identify pro- and anti-inflammatory cytokines associated with AD in the Malaysian population.
  
  
  METHODS
  Further to informed consent from 39 healthy subjects and 39 probable AD patients, 8.5 mL of peripheral blood was collected and serum was extracted. The differential levels of 12 serum cytokines extracted from peripheral blood samples were measured using Procarta Multiplex Cytokine and enzyme-linked immunoassay kits. Concentrations of cytokines were measured at 615 nm using a fluorometer.
  
  
  RESULTS
  Except for tumor necrosis factor-α, all classical pro-inflammatory cytokines (interleukin [IL]-1β, IL-6, IL-12 and interferon-γ) were found to be significantly upregulated (P < 0.001) in AD patients. Three of the five non-classical pro-inflammatory cytokines (C-X-C motif ligand 10 [CXCL-10], monocyte chemoattractant protein-1 and macrophage inflammatory protein-1α) showed similar patterns. Both classical IL-10 and non-classical IL-13 anti-inflammatory cytokines were significantly downregulated (P < 0.001) in AD patients when compared with non-AD controls. Receiver operating characteristic curve analyses for both CXCL-10 (IP-10) and IL-13 showed a high level of diagnostic accuracy (area under curve = 1 [95% confidence interval]). Both CXCL-10 and IL-13 also showed sensitivity of 100% and specificity of 100% for diagnosis of AD (cut-off values >53.65 ρg/mL and <9.315 ρg/mL, respectively).
  
  
  CONCLUSIONS
  Both the non-classical pro-inflammatory CXCL-10 and anti-inflammatory IL-13 cytokines showed promising potential as blood-based cytokine biomarkers for AD. This is the first study of non-classical cytokine profiles of Malaysian AD patients. Geriatr Gerontol Int 2017; 17: 839-846.
authors.affiliation: Faculty of Pharmacy, Universiti Teknologi MARA, Selangor, Malaysia.|Collaborative Drug Discovery Research Group, Pharmaceutical and Life Sciences Community of Research, Universiti Teknologi MARA, Selangor, Malaysia.
authors.forename: Dayana Sazereen
authors.initials: DS
authors.lastname: Mohd Hasni
authors.affiliation: Faculty of Pharmacy, Universiti Teknologi MARA, Selangor, Malaysia.|Collaborative Drug Discovery Research Group, Pharmaceutical and Life Sciences Community of Research, Universiti Teknologi MARA, Selangor, Malaysia.
authors.forename: Siong Meng
authors.initials: SM
authors.lastname: Lim
authors.affiliation: Division of Geriatric Medicine, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Ai Vyrn
authors.initials: AV
authors.lastname: Chin
authors.affiliation: Division of Geriatric Medicine, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Maw Pin
authors.initials: MP
authors.lastname: Tan
authors.affiliation: Division of Geriatric Medicine, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Philip Jun Hua
authors.initials: PJH
authors.lastname: Poi
authors.affiliation: Division of Geriatric Medicine, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Shahrul Bahyah
authors.initials: SB
authors.lastname: Kamaruzzaman
authors.affiliation: Faculty of Pharmacy, Universiti Teknologi MARA, Selangor, Malaysia.|Brain Degeneration and Therapeutics Group, Pharmaceutical and Life Sciences Community of Research, Universiti Teknologi MARA, Selangor, Malaysia.
authors.forename: Abu Bakar Abdul
authors.initials: ABA
authors.lastname: Majeed
authors.affiliation: Faculty of Pharmacy, Universiti Teknologi MARA, Selangor, Malaysia.|Collaborative Drug Discovery Research Group, Pharmaceutical and Life Sciences Community of Research, Universiti Teknologi MARA, Selangor, Malaysia.
authors.forename: Kalavathy
authors.initials: K
authors.lastname: Ramasamy
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D015415:Biomarkers / Q000097:blood; D016207:Cytokines / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005470:Fluorometry; D006801:Humans; D018793:Interleukin-13 / Q000097:blood*; D008296:Malaysia / Q000453:epidemiology; D008297:Male; D015995:Prevalence; D000075744:Receptors, CXCR6 / Q000097:blood*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D015415:Biomarkers; C106330:CXCR6 protein, human; D016207:Cytokines; D018793:Interleukin-13; D000075744:Receptors, CXCR6; D014409:Tumor Necrosis Factor-alpha
keywords: Alzheimer's disease; C-X-C motif ligand 10; cytokines; dementia; interleukin-13