scholarly journals Abnormal amyloid β 42 expression and increased oxidative stress in plasma of CKD patients with cognitive dysfunction: A small scale case control study comparison with Alzheimer's disease

BBA Clinical ◽  
2017 ◽  
Vol 8 ◽  
pp. 20-27 ◽  
Author(s):  
G. Vinothkumar ◽  
C. Kedharnath ◽  
S. Krishnakumar ◽  
S. Sreedhar ◽  
K. Preethikrishnan ◽  
...  
2021 ◽  
Vol 749 ◽  
pp. 135710
Author(s):  
Lifei Xu ◽  
Qiuping Dong ◽  
Liben Xu ◽  
Wei Zou ◽  
Hui Li

2012 ◽  
Vol 11 (11) ◽  
pp. 1389-1403 ◽  
Author(s):  
Romain Simon ◽  
Marion Girod ◽  
Catherine Fonbonne ◽  
Arnaud Salvador ◽  
Yohann Clément ◽  
...  

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.


Biomedicines ◽  
2020 ◽  
Vol 8 (11) ◽  
pp. 457 ◽  
Author(s):  
Vanesa Cantón-Habas ◽  
Manuel Rich-Ruiz ◽  
Manuel Romero-Saldaña ◽  
Maria del Pilar Carrera-González

Preventing the onset of dementia and Alzheimer’s disease (AD), improving the diagnosis, and slowing the progression of these diseases remain a challenge. The aim of this study was to elucidate the association between depression and dementia/AD and to identify possible relationships between these diseases and different sociodemographic and clinical features. In this regard, a case-control study was conducted in Spain in 2018–2019. The definition of a case was: A person ≥ 65 years old with dementia and/or AD and a score of 5–7 on the Global Deterioration Scale (GDS). The sample consisted of 125 controls; among the cases, 96 had dementia and 74 had AD. The predictor variables were depression, dyslipidemia, type 2 diabetes mellitus, and hypertension. The results showed that depression, diabetes mellitus, and older age were associated with an increased likelihood of developing AD, with an Odds Ratio (OR) of 12.9 (95% confidence interval (CI): 4.3–39.9), 2.8 (95% CI: 1.1–7.1) and 1.15 (95% CI: 1.1–1.2), respectively. Those subjects with treated dyslipidemia were less likely to develop AD (OR 0.47, 95% CI: 0.22–1.1). Therefore, depression and diabetes mellitus increase the risk of dementia, whereas treated dyslipidemia has been shown to reduce this risk.


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