%0 Journal Article
%T Oxidative Stress in Alzheimer¡¯s Disease: Why Did Antioxidant Therapy Fail?
%A Torbj£¿rn Persson
%A Bogdan O. Popescu
%A Angel Cedazo-Minguez
%J Oxidative Medicine and Cellular Longevity
%D 2014
%I Hindawi Publishing Corporation
%R 10.1155/2014/427318
%X Alzheimer¡¯s disease (AD) is the most common form of dementia in the elderly, with increasing prevalence and no disease-modifying treatment available yet. A remarkable amount of data supports the hypothesis that oxidative stress is an early and important pathogenic operator in AD. However, all clinical studies conducted to date did not prove a clear beneficial effect of antioxidant treatment in AD patients. In the current work, we review the current knowledge about oxidative stress in AD pathogeny and we suggest future paths that are worth to be explored in animal models and clinical studies, in order to get a better approach of oxidative imbalance in this inexorable neurodegenerative disease. 1. Introduction Alzheimer¡¯s disease (AD) is the most common form of dementia and was carried by an estimated 35.6 million people in 2010 [1]. The number is expected to increase to about 115 million sufferers in year 2050. The challenges in AD research today include discovering methods to diagnose patients in an earlier stage and to find new treatments to prevent or cure the disease. There are some inherited forms of the AD, also known as Familial Alzheimer¡¯s Disease (FAD), caused by mutations in one of these three genes: Amyloid Precursor Protein (APP), Presenilin-1, and Presenilin-2. These mutations are all linked to the overproduction of amyloidogenic forms of the amyloid-¦Â (A¦Â), a peptide that is generated by a sequential cleavage of APP by the ¦Â- and ¦Ã-secretases [2]. The majority of AD cases (more than 95%) are, however, sporadic and cannot be explained by deterministic mutations. It is hypothesised that sporadic AD results from a combination between environmental factors and risk genes. The most important risk gene is apolipoprotein E (ApoE), encoding an important molecule in lipid metabolism. ApoE has in humans three different isoforms, ¦Å2, ¦Å3, and ¦Å4. The ¦Å4 allele is associated with increased risk for AD, while ¦Å2 is considered to be protective. People with one copy of the ¦Å4 allele have approximately three times higher risk of getting the disease, while homozygotes have 12 times higher risk [3]. Symptoms of AD are characterized by progressive decline in cognitive abilities such as memory, mood, and behaviour, which leads to social and mental disability. The underlying pathophysiology of AD includes loss of neurons and synapses in the cerebral cortex and parts of the subcortical areas [4]. Apoptosis is thought to be one of the mechanisms that lead to cell death in AD [5, 6]. In addition to this, AD brains also harbour extracellular amyloid depositions
%U http://www.hindawi.com/journals/omcl/2014/427318/