Association of TLR4 with Alzheimer's disease risk and presymptomatic biomarkers of inflammation

PREVENT-AD Research Group

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: A coding variant in the TLR4 receptor (rs4986790), previously associated with longevity and Alzheimer's disease (AD) risk reduction, was examined in a population isolate (Québec Founder Population [QFP]) and in presymptomatic individuals with a parental history of AD (Pre-Symptomatic Evaluation of Novel or Experimental Treatment for Alzheimer's Disease [PREVENT-AD]). Methods: Genotyping was performed using the Illumina HumanHap 550k (QFP) and the Illumina Omni2.5 beadchips (PREVENT-AD). Cognition was assessed using the Repeatable Battery for Assessment of Neuropsychological Status (RBANS). Whole-brain cortical thickness data were analyzed using CIVET 1.12. Cerebrospinal fluid concentrations of cytokines were obtained by using Milliplex. Results: The minor allele of the rs4986790 polymorphism (G) is associated with a reduced risk of developing AD in the QFP, as well as higher visuospatial and constructional abilities, higher cortical thickness in visual-related regions, and stable cerebrospinal fluid IL-1β levels in the PREVENT-AD cohort. Discussion: The rs4986790 G coding variant in the TLR4 gene appears to reduce AD risk through the modulation of IL-1β synthesis and secretion in the presymptomatic phase of the disease.

Original languageEnglish (US)
Pages (from-to)951-960
Number of pages10
JournalAlzheimer's and Dementia
Volume15
Issue number7
DOIs
StatePublished - Jul 2019

Keywords

  • Alzheimer's disease
  • Cortical thickness
  • Frontal cortex
  • Fusiform gyrus
  • Genetics
  • IL-1β
  • Inflammation
  • Occipital cortex
  • TLR4
  • Visuospatial and constructional abilities

ASJC Scopus subject areas

  • Epidemiology
  • Health Policy
  • Developmental Neuroscience
  • Clinical Neurology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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