scholarly journals Val66Met Polymorphism in BDNF Has No Sexual and APOE ε4 Status-Based Dimorphic Effects on Susceptibility to Alzheimer’s Disease: Evidence From an Updated Meta-Analysis of Case–Control Studies and High-Throughput Genotyping Cohorts

2017 ◽  
Vol 33 (1) ◽  
pp. 55-63 ◽  
Author(s):  
Qingnan Zhao ◽  
Yaqi Shen ◽  
Yanli Zhao ◽  
Lining Si ◽  
Shan Jiang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
High Throughput ◽  
Meta Analysis ◽  
Case Control ◽  
Case Control Studies ◽  
Val66met Polymorphism ◽  
Apoe Ε4

Interleukin-1A −889C/T polymorphism and risk of Alzheimer’s disease: a meta-analysis based on 32 case–control studies

2012 ◽  
Vol 259 (8) ◽  
pp. 1519-1529 ◽  
Author(s):  
Xue Qin ◽  
Qiliu Peng ◽  
Zhiyu Zeng ◽  
Zhiping Chen ◽  
Liwen Lin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Meta Analysis ◽  
Case Control ◽  
Case Control Studies

scholarly journals Homocysteine and Folic Acid: Risk Factors for Alzheimer's Disease—An Updated Meta-Analysis

2021 ◽  
Vol 13 ◽  
Author(s):  
Qianwen Wang ◽  
Jingjing Zhao ◽  
Hongtao Chang ◽  
Xu Liu ◽  
Ruixia Zhu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Folic Acid ◽  
Cohort Studies ◽  
Prospective Cohort ◽  
Meta Analysis ◽  
Case Control ◽  
Case Control Studies ◽  
Prospective Cohort Studies ◽  
Increased Risk

Background: Recent studies have reported that homocysteine (Hcy) may play a vital role in the pathogenesis of vascular dementia (VaD) and Alzheimer's disease (AD). Our study explored the relationship between the plasma Hcy and folate levels and the risk of dementia.Methods: We searched Embase, PubMed, and Web of Science for published literature, including case-control studies and prospective cohort studies, and performed a systematic analysis.Results: The results of our meta-analysis, consisting of case-control studies, showed higher levels of Hcy and lower levels of folate in dementia, AD, and VaD patients than those in non-demented controls (for dementia: SMD = 0.812, 95% CI [0.689, 0.936], p = 0.000 for Hcy; SMD = −0.677, 95% CI [−0.828, −0.525], p = 0.000 for folate). AD patients showed significantly lower plasma Hcy levels compared to VaD patients (SMD = −0.278, 95% CI [−0.466, −0.09], p = 0.000). Subgroup analysis revealed that ethnicity, average age, and dementia type had no significant effect on this association. Furthermore, from the analysis of prospective cohort studies, we identified that elevated plasma Hcy levels were associated with an increased risk of dementia, AD, and VaD (RRdementia = 1.22, 95% CI [1.08, 1.36]; RRAD = 1.07, 95% CI [1.04, 1.11]; RRVaD = 1.13, 95% CI [1.04, 1.23]). In addition, every 5 μmol/L increase in the plasma Hcy level was associated with a 9% increased risk of dementia and a 12% increased risk of AD.Conclusion: Hcy and folic acid are potential predictors of the occurrence and development of AD. A better understanding of their function in dementia could provide evidence for clinicians to rationalize clinical intervention strategies.

scholarly journals Alzheimer’s Disease and HLA-A2: Linking Neurodegenerative to Immune Processes through an In Silico Approach

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Ricardo A. Cifuentes ◽  
Juan Murillo-Rojas
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Interactions ◽  
In Silico ◽  
Meta Analysis ◽  
Specific Antigen ◽  
Case Control ◽  
Interacting Proteins ◽  
Protein Protein Interactions ◽  
Case Control Studies

There is a controversial relationship between HLA-A2 and Alzheimer’s disease (AD). It has been suggested a modifier effect on the risk that depends on genetic loadings. Thus, the aims of this study were to evaluate this relationship and to reveal genes associated with both concepts the HLA-A gene and AD. Consequently, we did first a classical systematic review and a meta-analysis of case-control studies. Next, by means of an in silico approach, we used experimental knowledge of protein-protein interactions to evaluate the top ranked genes shared by both concepts, previously found through text mining. The meta-analysis did not show a significant pooled OR (1.11, 95% CI: 0.98 to 1.24 in Caucasians), in spite of the fact that four of the included studies had a significant OR > 1 and none of them a significant OR < 1. In contrast, the in silico approach retrieved nonrandomly shared genes by both concepts (P= 0.02), which additionally encode truly interacting proteins. The network of proteins encoded byAPP, ICAM-1, ITGB2, ITGAL, SELP, SELL, IL2, IL1B, CD4, andCD8Alinked immune to neurodegenerative processes and highlighted the potential roles in AD pathogenesis of endothelial regulation, infectious diseases, specific antigen presentation, and HLA-A2 in maintaining synapses.

scholarly journals Total ApoE and ApoE4 Isoform Assays in an Alzheimer's Disease Case-control Study by Targeted Mass Spectrometry (n = 669): A Pilot Assay for Methionine-containing Proteotypic Peptides

2012 ◽  
Vol 11 (11) ◽  
pp. 1389-1403 ◽  
Author(s):  
Romain Simon ◽  
Marion Girod ◽  
Catherine Fonbonne ◽  
Arnaud Salvador ◽  
Yohann Clément ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Case Control Study ◽  
Case Control ◽  
Performic Acid ◽  
Protein Levels ◽  
Apoe Ε4 ◽  
Ε4 Allele ◽  
Control Study

Allelic polymorphism of the apolipoprotein E (ApoE) gene (ApoE ε2, ApoE ε3 and ApoE ε4 alleles) gives rise to three protein isoforms (ApoE2, ApoE3 and ApoE4) that differ by 1 or 2 amino acids. Inheritance of the ApoE ε4 allele is a risk factor for developing Alzheimer's disease (AD). The potential diagnostic value of ApoE protein levels in biological fluids (i.e. cerebrospinal fluid, plasma and serum) for distinguishing between AD patients and healthy elderly subjects is subject to great controversy. Although a recent study reported subnormal total ApoE and ApoE4 levels in the plasma of AD patients, other studies have found normal or even elevated protein levels (versus controls). Because all previously reported assays were based on immunoenzymatic techniques, we decided to develop an orthogonal assay based on targeted mass spectrometry by tracking (i) a proteotypic peptide common to all ApoE isoforms and (ii) a peptide that is specific for the ε4 allele. After trypsin digestion, the ApoE4-specific peptide contains an oxidation-prone methionine residue. The endogenous methionine oxidation level was evaluated in a small cohort (n = 68) of heterozygous ε3ε4 carriers containing both healthy controls and AD patients. As expected, the proportion of oxidized residues varied from 0 to 10%, with an average of 5%. We therefore developed a standardized strategy for the unbiased, absolute quantification of ApoE4, based on performic acid oxidization of methionine. Once the sample workflow had been thoroughly validated, it was applied to the concomitant quantification of total ApoE and ApoE4 isoform in a large case-control study (n = 669). The final measurements were consistent with most previously reported ApoE concentration values and confirm the influence of the different alleles on the protein expression level. Our results illustrate (i) the reliability of selected reaction monitoring-based assays and (ii) the value of the oxidization step for unbiased monitoring of methionine-containing proteotypic peptides. Furthermore, a statistical analysis indicated that neither total ApoE and ApoE4 levels nor the ApoE/ApoE4 ratio correlated with the diagnosis of AD. These findings reinforce the conclusions of previous studies in which plasma ApoE levels had no obvious clinical significance.

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