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

PREVENT-AD Research Group

Research output: Contribution to journalArticle

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)
JournalAlzheimer's and Dementia
DOIs
StatePublished - Jan 1 2019

Fingerprint

Alzheimer Disease
Biomarkers
Inflammation
Interleukin-1
Population
Cerebrospinal Fluid
Asymptomatic Diseases
Toll-Like Receptor 4
Aptitude
Risk Reduction Behavior
Cognition
Alleles
Cytokines
Brain
Genes

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
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health

Cite this

Association of TLR4 with Alzheimer's disease risk and presymptomatic biomarkers of inflammation. / PREVENT-AD Research Group.

In: Alzheimer's and Dementia, 01.01.2019.

Research output: Contribution to journalArticle

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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 (Qu{\'e}bec 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.",
keywords = "Alzheimer's disease, Cortical thickness, Frontal cortex, Fusiform gyrus, Genetics, IL-1β, Inflammation, Occipital cortex, TLR4, Visuospatial and constructional abilities",
author = "{PREVENT-AD Research Group} and Justin Miron and Cynthia Picard and Lafaille-Magnan, {Marie {\'E}lyse} and M{\'e}lissa Savard and Anne Labont{\'e} and Breitner, {John C.S.} and Pedro Rosa-Neto and Daniel Auld and Judes Poirier",
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AU - PREVENT-AD Research Group

AU - Miron, Justin

AU - Picard, Cynthia

AU - Lafaille-Magnan, Marie Élyse

AU - Savard, Mélissa

AU - Labonté, Anne

AU - Breitner, John C.S.

AU - Rosa-Neto, Pedro

AU - Auld, Daniel

AU - Poirier, Judes

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