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Alzheimers Dement. 2019 Jul;15(7):951-960. doi: 10.1016/j.jalz.2019.03.012. Epub 2019 Jun 4.

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

Author information

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.

KEYWORDS:

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

PMID:
31175027
DOI:
10.1016/j.jalz.2019.03.012

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