title: Increased expressions of TLR2 and TLR4 on peripheral blood mononuclear cells from patients with Alzheimer's disease.
abstract: BACKGROUND
  Toll-like receptors 2 (TLR2) and TLR4 are involved in the microglia-mediated inflammatory response, Aβ plaque formation and Aβ clearance in Alzheimer's disease (AD). Our previous studies have shown that variants in the TLR2 and TLR4 genes are associated with the risk of AD. Therefore, we hypothesize that there may be significant changes in TLR2 and TLR4 expressions on peripheral blood mononuclear cells (PBMCs) from patients with AD when compared to healthy control subjects.
  
  
  METHODS
  Sixty patients with late-onset AD (LOAD) and 60 healthy controls matched for sex and age were recruited. Flow cytometry (FCM) was used to detect expressions of TLR2 and TLR4 proteins and real-time quantitative RT-PCR was performed to determine TLR2 and TLR4 mRNAs.
  
  
  RESULTS
  Compared with controls, expressions of TLR2 and TLR4 mRNAs were up-regulated in LOAD patients (TLR2/beta-actin mRNA: 0.390±0.204 versus 0.281±0.167, P<0.01; TLR4/beta-actin mRNA: 0.503±0.195 versus 0.322±0.183, P<0.01). The proteins levels were higher in LOAD patients than in controls (TLR2: 97.12±1.67% versus 41.07±18.44%, P<0.01, TLR4: 66.56±23.74% versus 14.83±4.31, P<0.01). In both cases, either AD or control group, TLR2 and TLR4 mRNAs expressions were positively correlated with the levels of proteins (TLR2: r=0.980 and 0.976,P<0.01; TLR4: r=0.938 and 0.970, P<0.01), respectively. There were significant negative correlations between TLR levels and MMSE score (TLR2: r=-0.32; P=0.01; TLR4: r=-0.29; P=0.02). In addition, CC genotype can increase the expression of TLR4 in AD patients.
  
  
  CONCLUSIONS
  This study gives the first evidence that expressions of TLR2 and TLR4 in PBMCs were markedly elevated in LOAD patients.
authors.affiliation: Department of Neurology, Shandong University, Jinan, Shandong Province, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Li-Zhu
authors.initials: LZ
authors.lastname: Wang
authors.forename: Jin-Tai
authors.initials: JT
authors.lastname: Yu
authors.forename: Zhao-Fu
authors.initials: ZF
authors.lastname: Chi
authors.forename: Lan
authors.initials: L
authors.lastname: Tan
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism* / Q000473:pathology; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics*
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4