Featured ArticleAssociation of TLR4 with Alzheimer's disease risk and presymptomatic biomarkers of inflammation
Section snippets
Background
Alzheimer's disease (AD) pathology is characterized by extracellular amyloid plaques [1], neuronal and synaptic loss [2], [3], intraneuronal neurofibrillary tangles [4], cortical thinning in the temporal, orbitofrontal, and parietal regions [5], and chronic inflammation [6]. New evidence suggests an association of inflammatory markers at midlife with worst performance on a word-recall test and lower brain volume in pathology-affected regions in AD [7]. Moreover, a recent study analyzing data
QFP cohort
In the QFP, the living AD subjects were 65 years or older and were diagnosed with probable AD based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria. The living age-matched control cases were also 65 years or older. These control cases were asymptomatic at the time of their recruitment based on the Mini-Mental State Examination score (adjusted for age and education >26) and the Montréal Cognitive Assessments (adjusted for education >26) [20]. Autopsied
Demographic characteristics of the AD subjects from the QFP cohort
Table 1 summarizes the demographic characteristics of the 44 AD brain samples obtained from the QFP cohort as a function of the rs4986790 variant (28 carriers of the AA genotype and 16 AG carriers). Owing to the low frequency of GG genotypes in this population, no GG carrier was present in our sample. There is no significant difference for age, gender distribution, postmortem interval, and APOE4 prevalence between AA and AG carriers.
Demographic characteristics of PREVENT-AD participants
Table 2 summarizes the demographic characteristics of the 136
Discussion
Recent evidence has revealed that inflammation might be a key player in prodromal AD [7], [9], [26]. Among the numerous actors implicated in the inflammatory process in AD, TLR4 has been identified as an important link between AD pathological processes and the downstream release of proinflammatory cytokines in both mouse models of AD [11], [12], [14], [27] and in human diseased brains [28]. In the last decade, the Asp299Gly coding variant (rs4986790) in the extracellular domain of TLR4 was
Acknowledgments
This study was supported by the Canadian Institutes of Health Research (MOP-119321), the Natural Sciences and Engineering Research Council of Canada (RGPIN-2015-03790), the J.-Louis Lévesque Foundation, the Lemaire Family Foundation, the McGill University and Genome Québec Innovation Centre, and the ICAO Charity Drive. Justin Miron and Cynthia Picard were supported by the Centre for Studies in the Prevention of Alzheimer's disease. Justin Miron was also supported by the Djavad Mowafaghian
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2022, International ImmunopharmacologyCitation Excerpt :Some research discovers that TLR4 expression increases in the brain tissues of AD patients. However, the activation and amplification of TLR4 signal should be mediated by MyD88 [8–9]. In inflammatory response, TLR4 is activated and binds to MyD88, so as to activate the downstream interleukin receptor associated kinase (IRAK) [10] and tumor necrosis factor receptor associated factor 6 (TRAF6), thus further activating the nuclear factor kappa-B (NF-κB) signal [11–12].