Lag-time in Alzheimer's disease patients: A potential plasmatic oxidative stress marker associated with ApoE4 isoform

Abstract

In the brain, Oxidative Stress (OS) contribute to structural and functional changes associated with vascular aging, such as endothelial dysfunction, extracellular matrix degradation, resulting in age-related reduced vasodilatation in response to agonists. For this reason, OS is considered a key factor in Alzheimer's Disease (AD) development and recent evidence correlated oxidative stress with vascular lesion in the pathogenesis of AD, but the mechanism still need to be fully clarified. The etiology of AD is still not completely understood and is influenced by several factors including Apolipoprotein E (ApoE) genotype. In particular, the Apo ϵ4 isoform is considered a risk factor for AD development. This study was aimed to evaluate the possible relationship between three plasmatic OS marker and Apo ϵ4 carrier status. Plasmatic soluble receptor for advanced glycation end products (sRAGE) levels, plasma antioxidant total defenses (by lag-time method) and plasmatic Reactive Oxygen species (ROS) levels were evaluated in 25 AD patients and in 30 matched controls. ROS were significantly higher while plasma antioxidant total defenses and sRAGE levels were significantly lower in AD patients compared to controls. In AD patients lag-time values show a significant positive linear correlation with sRAGE levels and a (even not significant) negative correlation with ROS levels. Lag-time is significantly lower in ϵ4 carrier (N = 13) than in ϵ4 non-carrier (N = 12). Our result confirms the substantial OS in AD. Lag-time levels showed a significant positive correlation with sRAGE levels and a significant association with ϵ4 carrier status suggesting that plasmatic lag-time evaluation can be considered as a potential useful OS risk marker in AD.