Association of PS1 Gene Polymorphisms with Alzheimer’s Disease in Chinese Population: A Meta-Analysis of Case-Control Studies

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.

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

BioMed Research International ◽

10.1155/2014/791238 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 4

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.

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