title: Serum IL-8 is a marker of white-matter hyperintensities in patients with Alzheimer's disease.
abstract: BACKGROUND
  Neuroinflammation and cerebrovascular disease (CeVD) have been implicated in cognitive impairment and Alzheimer's disease (AD). The present study aimed to examine serum inflammatory markers in preclinical stages of dementia and in AD, as well as to investigate their associations with concomitant CeVD.
  
  
  METHODS
  We performed a cross-sectional case-control study including 96 AD, 140 cognitively impaired no dementia (CIND), and 79 noncognitively impaired participants. All subjects underwent neuropsychological and neuroimaging assessments, as well as collection of blood samples for measurements of serum samples interleukin (IL)-6, IL-8, and tumor necrosis factor α levels. Subjects were classified as CIND or dementia based on clinical criteria. Significant CeVD, including white-matter hyperintensities (WMHs), lacunes, and cortical infarcts, was assessed by magnetic resonance imaging.
  
  
  RESULTS
  After controlling for covariates, higher concentrations of IL-8, but not the other measured cytokines, were associated with both CIND and AD only in the presence of significant CeVD (CIND with CeVD: odds ratios [ORs] 4.53; 95% confidence interval [CI] 1.5-13.4 and AD with CeVD: OR 7.26; 95% CI 1.2-43.3). Subsequent multivariate analyses showed that among the types of CeVD assessed, only WMH was associated with higher IL-8 levels in CIND and AD (WMH: OR 2.81; 95% CI 1.4-5.6).
  
  
  CONCLUSIONS
  Serum IL-8 may have clinical utility as a biomarker for WMH in AD. Longitudinal follow-up studies would help validate these findings.
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge, Singapore.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge, Singapore.
authors.forename: Yuek Ling
authors.initials: YL
authors.lastname: Chai
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge, Singapore; Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Radiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Saima
authors.initials: S
authors.lastname: Hilal
authors.affiliation: Department of Radiology, Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Neurology, Erasmus University Medical Center, Rotterdam, The Netherlands; Memory Aging and Cognition Centre, National University Health System, Kent Ridge, Singapore.
authors.forename: M Kamran
authors.initials: MK
authors.lastname: Ikram
authors.affiliation: Memory Aging and Cognition Centre, National University Health System, Kent Ridge, Singapore; Raffles Neuroscience Centre, Raffles Hospital, Singapore, Singapore.
authors.forename: Narayanaswamy
authors.initials: N
authors.lastname: Venketasubramanian
authors.affiliation: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge, Singapore.
authors.forename: Boon-Seng
authors.initials: BS
authors.lastname: Wong
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge, Singapore; Memory Aging and Cognition Centre, National University Health System, Kent Ridge, Singapore.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge, Singapore; Memory Aging and Cognition Centre, National University Health System, Kent Ridge, Singapore.
authors.forename: Mitchell K P
authors.initials: MK
authors.lastname: Lai
keywords: Alzheimer's disease; Cerebrovascular disease; Cognitive impairment; Dementia; IL-8; Inflammation; White-matter hyperintensities