ReviewFree radicals in Alzheimer's disease: Lipid peroxidation biomarkers
Introduction
Alzheimer's Disease (AD) is the most common cause of dementia worldwide. It is clinically characterized by progressive memory loss, and it is the most common form of pathologic neurodegeneration [1]. In general, AD incidence increases dramatically after 65 years old, and the number of AD patients is expected to increase considerably in the coming years [1,2]. In this sense, AD would have a great socio-economic impact [3]. Regarding AD physiopathology, it is characterized by two histological traces in brain: β-amyloid peptide forming senile plaques as extracellular deposits; and hyperphosphorylated tau protein forming neurofibrillary tangles as intracellular deposits [4]. Many risk factors have been associated with AD development. Genetic factors are some of them, but most of the AD cases are sporadic, and < 1% have a specific genetic cause [5]. Clinical evolution of AD can be divided in three phases: i) Preclinical AD, in which individuals conserve cognitive capacity but different biomarkers could be altered; ii) Mild cognitive impairment (MCI), when affected individuals show the first symptoms of cognitive impairment, the most common of which being episodic memory loss; iii) Dementia, when cognitive impairment affects the ability to carry out daily activities in an independent way, and individuals suffer from behaviour changes [6].
Section snippets
Free radicals in Alzheimer's disease
Free radicals chemistry is attracting attention because of its relationship with human diseases. Specifically, an excess of free radicals, such as reactive oxygen species (ROS) and reactive nitrogen species (RNS), are generated under pathological AD conditions [7], triggering an imbalance between free radical production and antioxidants mechanisms, known as oxidative stress condition.
Oxidative stress has been related to neurodegenerative pathologies and aging, so it could also play a
Lipid peroxidation in Alzheimer's disease
Oxidative stress causes damage to biomolecules (proteins, lipid, DNA…) forming several oxidized molecules (carbonyls, peroxides, strand breaks…). The oxidative damage to lipids by ROS results in the formation of lipid peroxidation products, as depicted in Fig. 1. These lipid peroxidation products can be classified depending on the modified lipid. Thus, isoprostanes/isofurans are produced from arachidonic acid oxidation (all tissues), neuroprostanes/neurofurans from docosahexanoic acid oxidation
Conclusions
Recent research has focused on the link between free radicals and the formation of β-amyloid aggregates in AD development. In this sense, there is a large controversy regarding the consideration of free radicals as an AD cause or consequence. In any case, it seems clear that oxidative stress and, specifically, lipid peroxidation, are molecular pathways involved in early AD development. Therefore, this relationship could be useful for AD diagnosis and treatment monitoring.
As AD potential
Acknowledgements
CC-P acknowledges a post-doctoral “Miguel Servet I” Grant (CP16/00082) from the Health Research Institute Carlos III (Spanish Ministry of Economy and Competitiveness), and the European Regional Development Fund (FEDER).
CP-B acknowledges a pre-doctoral Grant (associated to “Miguel Servet” project CP16/00082) from the Health Research Institute Carlos III (Spanish Ministry of Economy, Industry and Competitiveness).
The authors are grateful for the professional English language editing to Mr. Arash
Conflict of interest
The authors report no conflict of interest.
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