Association of TLR4 with Alzheimer's disease risk and presymptomatic biomarkers of inflammation.
|Title||Association of TLR4 with Alzheimer's disease risk and presymptomatic biomarkers of inflammation.|
|Publication Type||Journal Article|
|Year of Publication||2019|
|Authors||Miron J, Picard C, Lafaille-Magnan M-E, Savard M, Labonte A, Breitner JCS, Rosa-Neto P, Auld D, Poirier J|
|Corporate Authors||PREVENT-AD Research Group|
|Date Published||2019 Jul|
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.
|Alternate Journal||Alzheimers Dement|