Antioxidant Status andAPOEGenotype As Susceptibility Factors for Neurodegeneration in Alzheimer's Disease and Vascular Dementia

Abstract

Different factors interact to develop neurodegeneration in patients with dementia and other neurodegenerative disorders. Oxidative stress and the e4 allele of apolipoprotein E (ApoE) are associated with significant alteration in lipid metabolism, in turn connected to a variety of neurodegenerative diseases and aging. Thus, a better understanding of the pathogenetic pathways associated with lipid dyshomeostasis may elucidate the causes of neurodegenerative processes. To address this issue, we evaluated the effects of antioxidant status and APOE genotype on neurodegeneration in patients with dementia of the Alzheimer type (AD), with vascular dementia (VaD), and in elderly healthy controls. Eighty-two AD, 42 VaD patients, and 26 healthy controls were recruited and underwent medial temporal lobe atrophy (MTA) assessment, white matter hyperintensities rating (WMH), serum total antioxidant status assaying (TAS), and APOE genotyping. A logistic regression algorithm applied to our data revealed that a 0.01 mmol/L decrease of TAS concentration increased the probability of MTA by 24% ( p = 0.038) and that carriers of the APOE e4 allele showed higher WMH scores ( p = 0.018), confirming that small variations in antioxidant systems homeostasis are associated with relevant modifications of disease risk. Furthermore, in individuals with analogous TAS values, the presence of the e4 allele increased the predicted probability of having MTA. These outcomes further sustain the interaction of oxidative stress and APOE genotype to neurodegeneration.

Assessment of Possible Association Between Antioxidant Levels and Apoe Gene Polymorphism in Demented Saudi Population

“…These findings support the hypothesis that demonstrate the presence of E4 allele and decline antioxidant level with elevated lipid peroxidation are independent risk factors for dementia. and they are contribute to the pathogenic cascade in dementia by different pathways (Ihara et al, 2000;Zito et al, 2013;López-Riquelme et al, 2016). In conclusion, our study indicated that the APOE4 allele and oxidative stress are separated risk factor in the pathogenesis of dementia in the Saudi population.…”

“…While some studies have shown that APOE4 is positively associated with markers of oxidative stress and negatively associated with antioxidant defense markers compared to APOE3 and APOE2 (Chico et al, 2013;Dose et al, 2016). Non significant differences was reported between the APOE isoforms and specific antioxidative properties by Zito et al (2013) and López-Riquelme et al (2016). The overall purpose of this research is to evaluate the possible relationship between APOE genotype and serum level of antioxidant in Saudi patients with dementia of different types.…”

“…On the other hand, the E2 and E3 isoforms possess greater antioxidant activity (Pulido et al, 2005;Baldeiras et al, 2008;Chico et al, 2013;Dose et al, 2016). Other studies showed that APOE genotype and oxidative stress or antioxidant activities are independent risk factors for dementia (Ihara et al, 2000;Zito et al, 2013;López-Riquelme et al, 2016).…”

Humanin: A Possible Linkage Between Alzheimer’s Disease and Type 2 Diabetes

“…Inflammatory mediators are responsible for certain pathophysiological changes in these diseases [3]. ApoE and lipid metabolism disorders have also been reported to be responsible for T2DM and metabolic syndrome [4]. ApoE, inflammation and lipid metabolism disorder are closely related to and are responsible for the main pathophysiological changes in AD patients.…”

Modeling Alzheimer's disease with non-transgenic rat models

“…Buthionine sulfoximine, an inhibitor of glutathione synthesis, was used to reduce the natural antioxidant defense of the brain and facilitate oxidative stress. Oxidative stress is a deleterious process that, since the late 1980s to early 1990s [61-63], has been unanimously recognized to play a role in AD pathogenesis [60]. It is generally admitted that oxidative species are generated either from, but not restricted to, neuroinflammation, mitochondria respiratory chain impairment [64,65] or from a direct effect of the amyloid peptide [66].…”