Justin Miron1, Cynthia Picard1, Marie-Élyse Lafaille-Magnan1, Mélissa Savard2, Anne Labonté2, John Breitner1, Pedro Rosa-Neto1, Daniel Auld3, Judes Poirier4. 1. Douglas Mental Health University Institute, Montréal, Québec, Canada; Centre for the Studies in the Prevention of Alzheimer's Disease, Montréal, Québec, Canada; McGill University, Montréal (Québec), Montréal, Québec, Canada. 2. Douglas Mental Health University Institute, Montréal, Québec, Canada; Centre for the Studies in the Prevention of Alzheimer's Disease, Montréal, Québec, Canada. 3. McGill University and Génome Québec Innovation Centre, Montréal, Québec, Canada. 4. Douglas Mental Health University Institute, Montréal, Québec, Canada; Centre for the Studies in the Prevention of Alzheimer's Disease, Montréal, Québec, Canada; McGill University, Montréal (Québec), Montréal, Québec, Canada. Electronic address: judes.poirier@mcgill.ca.
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.
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.
Authors: Yihan Li; Simon M Laws; Luke A Miles; James S Wiley; Xin Huang; Colin L Masters; Ben J Gu Journal: Cell Mol Life Sci Date: 2021-10-27 Impact factor: 9.207
Authors: Malena Dos Santos Guilherme; Victor F Zevallos; Aline Pesi; Nicolai M Stoye; Vu Thu Thuy Nguyen; Konstantin Radyushkin; Andreas Schwiertz; Ulrich Schmitt; Detlef Schuppan; Kristina Endres Journal: Int J Mol Sci Date: 2020-08-31 Impact factor: 5.923