Association of the C47T Polymorphism in SOD2 with Amnestic Mild Cognitive Impairment and Alzheimer's Disease in Carriers of the APOEε4 Allele.

David Gamarra,Manuel Fernández-Martínez,Marian M De Pancorbo,Xabier Elcoroaristizabal

doi:10.1155/2015/746329

David Gamarra, Manuel Fernández-Martínez + Show 2 more

Open Access

https://doi.org/10.1155/2015/746329

Copy DOI

Abstract

Oxidative stress plays an important part in amnestic mild cognitive impairment (aMCI), the prodromal phase of Alzheimer's disease (AD). Recent evidence shows that polymorphisms in the SOD2 gene affect the elimination of the reactive oxygen species (ROS) generated in mitochondria. The aim of this study was to determine whether the functional rs4880 SNP in the SOD2 gene is a risk factor associated with aMCI and sporadic AD. 216 subjects with aMCI, 355 with AD, and 245 controls have been studied. The SNP rs4880 of the SOD2 gene was genotyped by RT-PCR and the APOE genotype was determined by PCR and RFLPs. Different multinomial logistic regression models were used to determine the risk levels for aMCI and AD. Although the T allele of the SOD2 rs4880 SNP gene (rs4880-T) is not an independent risk for aMCI or AD, this allele increases the risk to aMCI patients carrying at least one APOEε4 allele. Moreover, rs4880-T allele and APOEε4 allele combination has been found to produce an increased risk for AD compared to aMCI reference patients. These results suggest that APOEε4 and rs4880-T genotype may be a risk for aMCI and a predictor of progression from aMCI to AD.

Highlights

The accumulation of beta-amyloid (Aβ) and tau proteins in the brain tissue of patients with Alzheimer’s disease (AD) is related to the loss of synapse and neuronal death
The T risk allele frequency of the rs4880 single nucleotide polymorphisms (SNPs) was 0.488 for amnestic mild cognitive impairment (aMCI) and 0.463 for AD, being similar to the frequency observed in the controls (0.480)
Significant differences between the aMCI, AD, and healthy control groups were not found in rs4880 polymorphism (p > 0.05)

Summary

Introduction

The accumulation of beta-amyloid (Aβ) and tau proteins in the brain tissue of patients with Alzheimer’s disease (AD) is related to the loss of synapse and neuronal death. The brains of patients with AD in its prodromal phase, with amnesiac mild cognitive impairment (aMCI), have shown significant oxidative damage [7,8,9,10] and it is suggested that this damage affects the nuclear DNA differently from the mitochondrial one, the latter being greater [11]. Peripheral oxidative stress biomarkers in AD patients have showed an increase in molecules such as carbonyl proteins [12], 3-nitrotyrosine [13], isoprostanes [14], DNA oxidation (8-oxoguanine) [15], and malonaldehyde (MDA) [16]. Higher MDA and carbonyl protein levels have been found in MCI [16, 17] reporting a clear evidence of oxidative damage in mild cognitive impairment too

Objectives

Methods

Results

Conclusion