Age Modifies the Association Between Apolipoprotein E Genotype and Alzheimer's Disease: A CSF Biomarker-Based Multicentric Case-Control Study

2019 ◽  
Author(s):  
Hana Sadikki ◽  
Aurore Fayosse ◽  
Emmanuel Cognat ◽  
Séverine Sabia ◽  
Sebastiaan Engelborghs ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Apolipoprotein E ◽  
Case Control Study ◽  
Case Control ◽  
Csf Biomarker ◽  
Control Study ◽  
Apolipoprotein E Genotype

Apolipoprotein E in Alzheimer's disease risk and case detection: A case-control study

1996 ◽  
Vol 49 (10) ◽  
pp. 1143-1148 ◽  
Author(s):  
Walter A. Kukull ◽  
Gerard D. Schellenberg ◽  
James D. Bowen ◽  
Wayne C. McCormick ◽  
Chang-En Yu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Apolipoprotein E ◽  
Case Control Study ◽  
Disease Risk ◽  
Case Control ◽  
Case Detection ◽  
Control Study

The MCP-1 A-2518G polymorphism increases the risk of Alzheimer’s disease: A case-control study

2021 ◽  
Vol 749 ◽  
pp. 135710
Author(s):  
Lifei Xu ◽  
Qiuping Dong ◽  
Liben Xu ◽  
Wei Zou ◽  
Hui Li
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Case Control Study ◽  
Case Control ◽  
Control Study

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.

Sign in / Sign up

Export Citation Format

Share Document