Oxidative Stress in Alzheimer’s Disease: Molecular Hallmarks of Underlying Vulnerability

Abstract

Alzheimer’s disease (AD) is the most common neurodegenerative disease characterized by the presence of senile plaques (SPs) and neurofibrillary tangles (NFTs) in the hippocampus and cortex of afflicted patients. In case of AD patients, during the progression of the disease, there is proof that brain tissues of these individuals are exposed to oxidative stress (OS). In AD, advanced glycation end products (AGEs) exist in amyloid plaques; moreover, accelerated oxidation of glycated proteins might cause its extracellular accumulation. AGEs have also found to take part in neuronal death, initiating production of free radical and therefore increasing OS. In case of progression of AD, emerging proof has shown that OS plays a key role. Nevertheless, the processes that ultimately cause disturbance of redox balance and also the sources of the free radicals are still unclear. Likewise, an excessive amount of reactive oxygen species (ROS) might be produced from processes including dysfunction of mitochondria and/or abnormal transition metal accumulation, though the redox imbalance seems to be promoted by the aberrant accumulation of amyloid s (Aβ) and tau proteins. For Aβ- and tau-mediated neurotoxicity, the resulted OS has been associated. There is also the availability of evidence that OS might increase the aggregation and production of Aβ and also assist the polymerization as well as phosphorylation of tau, therefore creating a malicious cycle that stimulates the progression and even initiation of Alzheimer’s. This chapter represents the critical pathogenic mechanism of OS and AD.