Genetic association of TLR4/11367 polymorphism with late-onset Alzheimer's disease in a Han Chinese population

Increased expressions of TLR2 and TLR4 on peripheral blood mononuclear cells from patients with Alzheimer's disease

“…We evidenced for the first time that TLR2 and TLR4 mRNAs were up-regulated and plasma levels of them were also higher in AD patients than in controls. Variants of TLR2 and TLR4 gene were thought to influence the susceptibility to AD [12][13][14][15]24,25]. Polymorphisms might affect the expression of the target gene and cytokine production of peripheral blood leukocytes by affecting the regulatory effect of the 3′ UTR of the TLR4 gene [26].…”

“…Polymorphisms might affect the expression of the target gene and cytokine production of peripheral blood leukocytes by affecting the regulatory effect of the 3′ UTR of the TLR4 gene [26]. In our previous study, we conducted an analysis about TLR4/11367 polymorphism and found that the minor allele (C) demonstrated a 2.67-fold risk for developing LOAD when compared with the G allele [13]. In the present study, we analyzed TLR4 plasma level in individuals with different genotypes and found that TLR4 level in AD patients with the GG genotype was significantly lower than that with CC genotype (P b 0.001), and that with GC (P b 0.001).…”

“…Some research revealed that variants in TLR2 and TLR4 genes were associated with risk of LOAD. For example, our previous two studies demonstrated that microsatellite polymorphisms of TLR2 can increase risk of LOAD [12] and TLR4/11367 polymorphism was associated with LOAD in a Han Chinese population [13]. Another two studies analyzed the association between AD and TLR4 +896A/G [14,15], that is a common adenine to guanine substitution in TLR4, causing the replacement of an aspartic acid residue by glycine at amino acid 299 (Asp299Gly).…”

Bioenergetic Dysfunction and Inflammation in Alzheimer’s Disease: A Possible Connection

“…Specific TLR9 polymorphisms have been associated with a decreased AD risk, while specific TLR4 polymorphisms have been associated with an increased risk (Balistreri et al, 2008; Wang et al, 2011, 2013). There is some conflict in the literature regarding the association of TLR2 genetic polymorphisms in AD (Yu et al, 2011a,b).…”

The role of the immune system in neurodegenerative disorders: Adaptive or maladaptive?

“…In studies of LOAD in both Italian and Han Chinese populations, two polymorphisms have been identified that occur at higher frequencies in AD verses healthy controls. Interestingly, both polymorphisms reduce the activity of TLR4 (Minoretti et al, 2006; Wang et al, 2011). A beneficial role of TLR4 is further supported by a recent study in which detoxified monophosphoryl lipid A (MPL), a TLR4 ligand, significantly improved AD-like pathology in APP/PS1 mice (Michaud et al, 2013b).…”