Ying-Li Wang

Circulating miR-125b as a biomarker of Alzheimer's disease.

BACKGROUND MicroRNAs (miRNAs) are endogenous small RNAs of 21-25 nucleotides that post-transcriptionally regulate gene expressions. Recently, circulating miRNAs have been reported as promising biomarkers for neurodegenerative disorders and processes affecting the central nervous system. This study was conducted to investigate the potential role of serum miRNAs as diagnostic biomarkers for Alzheimers disease (AD). METHODS Serum samples were obtained from 105 probable AD patients and 150 age- and gender-matched normal controls. The serum concentrations of miRNAs miR-9, miR-29a, miR-29b, miR-101, miR-125b, and miR-181c were measured with a real-time quantitative reverse transcriptase PCR (qRT-PCR) method. RESULTS We found both miR-125b and miR-181c were down-regulated while miR-9 was up-regulated in serum of AD patients compared with that of normal controls. Among the receiver operating characteristic (ROC) results, miR-125b alone showed its priority with a specificity up to 68.3% and a sensitivity of 80.8%. Importantly, miR-125b was correlated with the Mini Mental State Examination (MMSE) in AD patients. CONCLUSIONS Our results indicate that serum miR-125b may serve as a useful noninvasive biomarker for AD.

Nutrition and the risk of Alzheimer's disease.

Alzheimers disease (AD) is a progressive neurodegenerative disorder that accounts for the major cause of dementia, and the increasing worldwide prevalence of AD is a major public health concern. Increasing epidemiological studies suggest that diet and nutrition might be important modifiable risk factors for AD. Dietary supplementation of antioxidants, B vitamins, polyphenols, and polyunsaturated fatty acids are beneficial to AD, and consumptions of fish, fruits, vegetables, coffee, and light-to-moderate alcohol reduce the risk of AD. However, many of the results from randomized controlled trials are contradictory to that of epidemiological studies. Dietary patterns summarizing an overall diet are gaining momentum in recent years. Adherence to a healthy diet, the Japanese diet, and the Mediterranean diet is associated with a lower risk of AD. This paper will focus on the evidence linking many nutrients, foods, and dietary patterns to AD.

Triggering receptor expressed on myeloid cells 2 variant is rare in late-onset Alzheimer's disease in Han Chinese individuals

Recent studies have reported that a rare mutation of triggering receptor expressed on myeloid cells 2 gene (TREM2 [rs75932628-T]) has significantly increased the risk of late-onset Alzhemiers disease (LOAD) in European-descendent population. To date, no study has investigated the association between rare mutations of TREM2 and LOAD risk in non-European population. Here, we sequenced exon2 of TREM2 in the northern Han Chinese population consisting of 1133 patients with LOAD and 1159 control subjects. Although, 4 novel mutations (c.102G>A: Val34Val, c.330C>T: Cys110Cys, c.342T>C: His114His, and c.343G>A: Gly115Ser) were identified in patients with LOAD, none of them exhibited significant association with LOAD risk after Bonferroni correction. Most importantly, the previously reported rare variants in European-descendent population including rs75932628-T (predicted to cause an R47H substitution) were absent in our cohort. These findings suggest that mutations in exon2 of TREM2 were unlikely to play a key role in the susceptibility of LOAD in the northern Han Chinese population.

Increased Expression of TREM2 in Peripheral Blood of Alzheimer's Disease Patients

TREM2 has been reported to be associated with Alzheimers disease (AD). Here, we evaluated TREM2 mRNA and protein expressions in peripheral blood from AD patients and healthy controls. Higher levels of TREM2 mRNA (p = 0.002) and protein (p < 0.001) were identified in AD patients. We observed a significant correlation between TREM2 expressions and MMSE score (mRNA: r = -0.482, protein: r = -0.582; p < 0.01). According to ROC curve analysis, the diagnostic accuracy for TREM2 protein levels on monocytes was 70%, with the sensitivity and specificity 68% and 72%, respectively. Our results indicate that TREM2 might serve as a novel noninvasive biomarker for AD diagnosis.

Genetic variation in PICALM and Alzheimer's disease risk in Han Chinese

The current study was conducted to investigate the association of phosphatidylinositol-binding clathrin assembly protein gene (PICALM) with late-onset Alzheimers disease (LOAD) risk in Han Chinese. We first sequenced PICALM for variants in a small sample (n = 100), and the selected variants were then genotyped in a larger cohort (n = 2292). Sequencing analysis identified 16 variants within PICALM including 5 new variants with extreme low frequency in the northern Han Chinese population. However, in the subsequent genotyping, none showed a significant association with LOAD risk after Bonferroni correction. These findings implicate that PICALM might not play a major role in the genetic predisposition to LOAD in Han Chinese.

Decreased expression of CD33 in peripheral mononuclear cells of Alzheimer's disease patients.

Recently, two independent genome-wide association studies (GWAS) have identified CD33 gene, encoding cluster of differentiation 33 (CD33), as a genetic locus associated with Alzheimers disease (AD). It has been suggested that CD33 may contribute to AD pathogenesis by involving in inflammatory response, synaptic dysfunction and cell membrane processes. We analyzed the expressions of CD33 in peripheral blood mononuclear cells (PBMCs) in AD group and control group by real-time quantitative polymerase chain reaction and flow cytometry. Expression of CD33 mRNA was down-regulated in AD patients comparing to controls (p=0.001). The frequency of CD33 positive monocytes was also lower in AD patients than in controls (44.02 ± 22.17% versus 54.06 ± 21.86%, p=0.001). Moreover, we observed a correlation between CD33 positive monocytes levels and Mini Mental State Examination (MMSE) score (r=0.220, p<0.05). According to receiver operating characteristic (ROC) curve analysis, the diagnostic accuracy for CD33 alone is relatively lower, while, combining with additional parameters might further improve the diagnostic value for AD.

Toll-like receptor 9 promoter polymorphism is associated with decreased risk of Alzheimer’s disease in Han Chinese

BackgroundToll-like receptors (TLRs), as major innate immune mediators, may be involved in clearance of cerebral amyloid-β (Aβ) deposits. Recently, a novel TLR9 signaling pathway has been uncovered, which is functionally associated with the immune inflammatory response and reducing Aβ burden in Alzheimer’s disease (AD) mice. Therefore, TLR9 might represent a reasonable functional candidate gene for AD.FindingsOur study investigated 1,133 sporadic late-onset AD (LOAD) and 1,159 healthy controls matched for sex and age in a large Han Chinese population. One selected functional rs187084 polymorphism within the TLR9 gene was genotyped by polymerase chain reaction-ligase detection reaction in a case–control associated study. The TLR9 rs187084 variant homozygote GG was significantly associated with a decreased LOAD risk after adjusting for age, gender, and ApoE ϵ4 status by logistic regression analysis (P = 0.035). Our result showed significant evidence of the interaction of ApoE ϵ4 with rs187084. When we further stratified our data by the ApoE ϵ4 status, we detected significant differences in the genotype and allele distributions of rs187084 between LOAD patients and controls in ApoE ϵ4 carriers (P < 0.001, P = 0.003, respectively). Moreover, we examined TLR9 expression in peripheral blood monocytes by flow cytometry, and the GG genotype of the TLR9 rs187084 polymorphism was associated with a higher TLR9 expression than two other genotypes in LOAD patients.ConclusionOur findings support the hypothesis that the TLR9 polymorphism may modify LOAD risk in the Han Chinese population.