|Year : 2020 | Volume
| Issue : 2 | Page : 85-90
Simultaneous exposure to noise and carbon monoxide increases the risk of Alzheimer's disease: a literature review
Fereshteh Bagheri1, Vahid Rashedi2
1 Department of Audiology, School of Rehabilitation Sciences, Babol University of Medical Sciences, Mazandaran, Iran
2 School of Behavioral Sciences and Mental Health (Tehran Institute of Psychiatry), Iran University of Medical Sciences, Tehran, Iran
|Date of Submission||10-Jan-2020|
|Date of Acceptance||18-Feb-2020|
|Date of Web Publication||05-Jun-2020|
PhD Vahid Rashedi
School of Behavioral Sciences and Mental Health (Tehran Institute of Psychiatry), Iran University of Medical Sciences, Tehran
Source of Support: None, Conflict of Interest: None
Dementia is a syndrome of cognitive and functional decline, commonly occurring in later life as a result of neurodegenerative and cerebrovascular processes beginning earlier in the life course. An excess of free radicals has an essential role in neurodegenerative diseases and aging. This paper aims to review the effects of noise and carbon monoxide as a risk factor in Alzheimer's disease as well as the role of free radicals in the progress of Alzheimer's disease. Articles included in this review were identified through a search of the databases PubMed, Scopus, and Google Scholar using the search terms Alzheimer's disease, dementia, noise, reactive oxygen species, and Carbon Monoxide. The literature search was restricted to the years 1982 to 2020 and articles published in the English language. The metabolism rate of the body is very high when exposed to noise and carbon monoxide; this leads to overproduction of reactive oxygen species and oxidative stress conditions. Oxidative stress has an essential role in the mechanisms concerned in Alzheimer's disease. In addition to the consequences of noise and a chemical substance on the auditory system, they also have non-auditory effects that affect the brain and induced neurodegenerative disease.
Keywords: Alzheimer's disease; auditory system; carbon monoxide; dementia; free radicals; noise; older adults; oxidative stress; reactive oxygen species
|How to cite this article:|
Bagheri F, Rashedi V. Simultaneous exposure to noise and carbon monoxide increases the risk of Alzheimer's disease: a literature review. Med Gas Res 2020;10:85-90
|How to cite this URL:|
Bagheri F, Rashedi V. Simultaneous exposure to noise and carbon monoxide increases the risk of Alzheimer's disease: a literature review. Med Gas Res [serial online] 2020 [cited 2020 Jul 15];10:85-90. Available from: http://www.medgasres.com/text.asp?2020/10/2/85/285562
| Introduction|| |
Epidemiologic studies show that 11% of the world's population is over 60 years of age; this is projected to increase, by 2050, to 22% of the population. The most prevalence of aging is in the developing countries and the population of people living with Alzheimer's disease (AD) is predicted to reach 115 million by 2050. AD is a prevalent age-related neurodegenerative disease; it is the main cause of a decrease in cognitive performance. Environmental and lifestyle factors are the risk factors that contributing to this disease. Stress can affect cognitive functions, and loud noise exposure is an important external source of stress.
Noise is an auditory stimulus that adversely affects the health condition and has adverse effects on the activities and behaviors. Several studies have been shown that chronic exposure to noise involved several skills of auditory processing ability such as sustain attention, a short span of memory, and speech perception.,,
Moreover, exposure to a high level of noise causes an enhancement of stress hormones that affect brain. The adverse effects of noise on the auditory system depend on the level and duration of the exposure. Noise induce temporary threshold shift, which was suddenly created by exposure to excessive levels of sound and noise-induced permanent threshold shift that can be created by chronic exposure to high levels of sound.
Carbon monoxide (CO) is generated as a part of exhaled air in the normal metabolite of healthy body and exposure to low levels of CO has no neurotoxic effect, but chronic exposure to CO is considered as a factor related to the development of central nervous system impairments.
In this review, the researchers aim to examine the evidence of whether exposure to noise and CO can increase the risk of AD.
| Search Methods|| |
Of 298 primary articles, 99 potentially eligible articles were reviewed. Articles included in this review were identified through searching the databases of PubMed, Medline, Scopus, Google Scholar and Scientific Information Database using the search terms of Alzheimer's disease, Noise, Carbon monoxide, Free radical, and hearing stress oxidative. We considered the factors related to AD, such as noise and CO. The literature search was restricted to the years 1982 to 2020 and the English language. [Figure 1] shows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flowchart of study selection.
|Figure 1: Preferred Reporting Items for Systematic Reviews and Meta- Analyses (PRISMA) flowchart for the study selection.|
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| Results|| |
Noise as a stressor and induced reactive oxygen species
The need for the industry in diverse societies has led to the creation of various factories and industries, and industrialization has also led the workforce to be in constant contact with machinery and equipment. The effects of widespread use of machinery and equipment make people more vulnerable to workplace hazards, including noise, which is the most commonly damaging physical hazard in the workplace. Noise-induced hearing loss (NIHL) is one of the most common occupational injuries. In developed and developing countries, it is estimated that over 600 million people are exposed to excessive noise, with a significant proportion of them suffering from hearing loss or hearing loss shortly. NIHL after age-related hearing loss (or presbycusis) is the most common cause of hearing loss in older adults, and also NIHL is the most commonly reported occupational disease in the United States.
NIHL not only causes mechanical damage but also leads to metabolic changes. Several mechanical damages have been observed in the NIHL, such as the reduction of the number of synapse between hair cells and auditory nerve fibers in the cochlea, decrease of synaptic vesicles, and reduction of the size of the synapse body. Moreover, inflammation of the dendrites (accumulation of additional glomerular neurotransmitters due to glutamate in the inner hair cells synapse) and neuronal changes in the nucleus of the cochlea and to the superior olivary complex have been observed.
Metabolic disturbance after exposure to noise can increase the free radicals in the mitochondria. Free radicals are reactive substances that can be grown in our body by exposure to several risk factors such as smoking, air pollution, chronic exposure to noise, and chemical substances (e.g., CO).
Reducing the blood flow of the cochlea after the formation of free radicals due to exposure to noise causes a lack of oxygen in the cochlea, and all of these factors ultimately lead to apoptosis and cell death., In addition to the mentioned effects, exposure to environmental noise can induce psychosocial responses such as stress, anxiety, sleep disturbances, behavioral, and performance variation. There is some evidence based on the effects of background noise on the event-related potential concerning attentive and cognitive alterations.
Oxidative stress and also cytokine production increased after exposure to noise in the brain. The prenatal noise stress and even chronic exposure to noise caused an excess of amyloid β-peptide (Aβ) plaques and also increased the size of plaque across a lifetime.,, Aβ plaques have been implicated in AD.,,,,,,
Noise as a stressor factor has adverse effects on memory. Stress disturbed neuroanatomical in the brain, particularly in the hippocampus and induced changes in the size and number of neurons., The hippocampus has the leading role in memory. The loss of synapse and neurons in the hippocampus are the clinical features of AD. Also, neuroinflammation in the hippocampus and accumulation of reactive oxygen species (ROS) are the significant features of AD. So the stress caused by exposure to noise could increase the risk of AD.
Carbon monoxide exacerbates the effects of noise
CO is classified as an asphyxiant gas. The CO is a colorless, odorless, and tasteless, flammable gas produced by incomplete combustion of organic materials such as coal, wood, paper, and oil. Motor vehicles and industries are among the most critical sources of CO production in the environment. CO excessively produced where fuel engines are used in closed spaces with improper ventilation. Many workers simultaneously exposed to CO and noise in workplaces.
CO is considered as one of the most crucial air pollutants both in the environment and in industrial environments. It has been estimated that in some areas such as enclosed environments, road tunnels, car parks, and underground subways, CO levels can exceed 100 per parts of million. Vehicles in cities are the source of 60% of CO gas. CO level fluctuates depending on the season so that its amount is lower in the summer. Toxic gases in the air have adverse effects on the central nervous system. Animal studies have shown that chronic exposure to air pollution leads to a decrease in cognitive function and neuroinflammation, inflammation could contribute to AD-pathogenesis.
The combination of CO with hemoglobin causes arterial carboxyl hemoglobin that reduces the amount of oxygen in the tissues and organs of the body especially has a direct toxic effect on mitochondria with the prevention of Cytochrome oxidase [Figure 2] and leads to hypoxic brain damage. Chronic exposure to CO can lead to anoxia, migraine, fatigue, decreased physical function, dizziness, nausea, vomiting, visual impairment, auditory abnormalities, Parkinson's disease, heart ischemia, heart disease, and atherosclerosis. Loss of consciousness may appear when exposure to CO raises levels of carboxyl hemoglobin in the blood. Studies have been shown that exposure to high-dose CO has adverse effects on the central nervous system and leads to abnormal white matter levels or neuronal degeneration.,, All smokes contain CO that causes increased free radicals and damage to the cerebral cortex.
|Figure 2: Schematic representation of toxic direct effect of COHb on mitochondria|
Note: ADP: Adenosine diphosphate; ATP: adenosine triphosphate; CO: carbon monoxide; COHb: carboxyl hemoglobin; cyt C: cytochrome c; e: electron; FADH2: reduced form of flavin adenine dinucleotide; Hb: hemoglobin; I-V: complex I-V; NAD: nicotinamide adenine dinucleotide; NADH: reduced form of nicotinamide adenine dinucleotide; Pi: phosphoric acid; Q: coenzyme Q.
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The evidence demonstrated the relation between air pollution, noise, and cognitive decline and dementia risk.,
So the change of brain structure can cause earlier memory loss and onset of AD. The possible mechanisms of exposure to noise and CO in AD are shown in [Figure 3].
|Figure 3: The possible mechanisms of exposed to noise and CO in Alzheimer's disease.|
Note: Aβ: Amyloid β-peptide; CO: carbon monoxide; RNS: reactive nitrogen species; ROS: reactive oxygen species.
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Both human and animal studies have been shown the increasing impact of exposure to CO on NIHL., Their results showed that the level of ROS in the animals simultaneously exposed to CO and noise was significantly higher than that exposed to noise only. ROS is one of the most important free radicals. CO toxicity is also believed to result in tissue hypoxia and increased oxidative stress (due to the formation of free radicals in the brain and the inner ear), as well as increased glutamate secretion.
The relation between reactive oxygen species and
AD is a progressive age-related disorder that degenerates neurons of the central nervous system and is the most cause of memory loss., The decline of synapses, especially in the hippocampus causes the atrophy of the brain in an individual with AD.
Production of free radicals such as ROS and reactive nitrogen species and the reduction of defense mechanism antioxidants result in oxidative stress condition. Antioxidants are molecules that eliminate the ROS when high levels of ROS are accumulated.
Various studies have shown that there are several risk factors for the development of AD, such as smoking, alcohol, obesity, stress, cardiovascular disease, but all of these risk factors have the same root in that they increase oxidative stress. Oxidative stress has an essential role in the mechanisms concerned in AD.,,,,,,,, Oxidative stress occurs in the initial stages of the progression of AD, and accumulation of oxidative stress along with a decrease of antioxidant defense levels accelerates the advance process of AD.,,,, The brain sensitive to ROS more than other tissues because of the high consumption of oxygen in the brain, so oxidative stress contributes to brain injury.,,,, Besides, iron (Fe2+) ions that necessary for proper functions of the human brain are with a high level in the brain, and when this ions reacting with hydrogen peroxide (H2O2) take part in the fenton reaction and produced highly reactive hydroxyl radical (•OH).
Fe2+ + H2O2 → Fe3+ + •OH + OH– (2)
AD is one of the pathological conditions of the brain in which oxidative stress causes neuronal cell injury.,,, Free radicals can impose damage to the mitochondrial electron transfer complex, thus limiting the production of adenosine triphosphate and increasing the production of free radicals., Mitochondrial dysfunction has been shown in neurodegenerative disorders such as AD.,,, It is well demonstrated that mitochondrial are the main source of adenosine adenosine triphosphate production; in normal condition, 98% of oxygen is used to produce adenosine triphosphate, and 1–2% of remaining oxygen produce ROS such as superoxide anion (O2–). Under this normal condition, the antioxidative defense systems which contain intracellular enzymes (e.g., glutathione peroxidase, superoxide dismutase, and catalase) cope with ROS. But when the body is exposed to high levels of metabolism, this causes increased body oxygen consumption and then leads to OH and H2O2 production with very high reactivity. Therefore ROS overcome to the antioxidative defense systems and cause damage to the body.,, Noise and CO exposure is a condition capable of increasing the rate of metabolism of the body.
Insoluble Aβ plaques, neurofibrillary tangles, and synapse loss in the brain are an essential feature of AD. ROS leads to an excess of Aβ peptides and Aβ increase during AD progression.,, An increase in the markers of oxidative damage to proteins, DNA, RNA, and lipids peroxidation has been shown in the brain of Alzheimer's suffers.,,,, Also, inflammation and oxidative stress are strongly related that chronic inflammation can be triggered by rising levels of oxidative stress in AD., The antioxidative defense systems to cope with oxidative stress are very important. The brain is very vulnerable to free radical damage because of the low capacity of antioxidants, and the high content of polyunsaturated fatty acids. So this is the possibility that chronic stress (exposure to noise and CO) changed the structure and function of the brain at one hand, and involved memory on the other side. Perhaps if people know the effects on health outcomes of such an exposure to noise and CO, they would pay more attention to determining noise and CO acceptable levels both in working and in a living environment.
| Conclusion|| |
In addition to the consequences of noise and a chemical substance on the auditory system, they also have non-auditory effects that affect the brain and induced neurodegenerative disease. In this review article, we conclude that noise plus CO exposure lead to oxidative stress condition, which has a vital role in causing the AD. Given that a large number of workers are simultaneously exposed to high levels of CO and noise. Current engineering and management controls are not effective in preventing the complications caused by these factors. So the new solutions such as biochemical methods should be used to prevent these effects.
Both authors contributed to the study design and writing.
Conflicts of interest
The authors declare no potential conflict of interest on publishing this paper.
This work was supported by Iran University of Medical Sciences, Iran.
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| References|| |
Kanasi E, Ayilavarapu S, Jones J. The aging population: demographics and the biology of aging. Periodontol 2000
Sutherland GT, Chami B, Youssef P, Witting PK. Oxidative stress in Alzheimer's disease: primary villain or physiological by-product? Redox Rep
Bagheri F, Borhaninejad V, Rashedi V. Alzheimer's disease and hearing loss among older adults: a literature review. Int J Psychol Behav Sci
Sayre LM, Moreira PI, Smith MA, Perry G. Metal ions and oxidative protein modification in neurological disease. Ann Ist Super Sanita
Arnsten AF, Goldman-Rakic PS. Noise stress impairs prefrontal cortical cognitive function in monkeys: evidence for a hyperdopaminergic mechanism. Arch Gen Psychiatry
Sikandaner HE, Park SY, Kim MJ, Park SN, Yang DW. Neuroprotective effects of sildenafil against oxidative stress and memory dysfunction in mice exposed to noise stress. Behav Brain Res
Golmohammadi R, Darvishi E, Faradmal J, Poorolajal J, Aliabadi M. Attention and short-term memory during occupational noise exposure considering task difficulty. Appl Acoust
Jafari Z, Kolb BE, Mohajerani MH. Chronic traffic noise stress accelerates brain impairment and cognitive decline in mice. Exp Neurol
Jafari Z, Kolb BE, Mohajerani MH. Noise exposure accelerates the risk of cognitive impairment and Alzheimer's disease: Adulthood, gestational, and prenatal mechanistic evidence from animal studies. Neurosci Biobehav Rev
. 2019. doi: 10.1016/j.neubiorev.2019.04.001
Kurmis AP, Apps SA. Occupationally-acquired noise-induced hearing loss: a senseless workplace hazard. Int J Occup Med Environ Health
Queiroga CS, Vercelli A, Vieira HL. Carbon monoxide and the CNS: challenges and achievements. Br J Pharmacol
Fechter LD, Chen GD, Rao D. Chemical asphyxiants and noise. Noise Health
Alberti PW. Noise, the most ubiquitous pollutant. Noise Health
Nelson DI, Nelson RY, Concha-Barrientos M, Fingerhut M. The global burden of occupational noise-induced hearing loss. Am J Ind Med
Slepecky N, Chamberlain SC. Distribution and polarity of actin in the sensory hair cells of the chinchilla cochlea. Cell Tissue Res
Fridberger A, Flock A, Ulfendahl M, Flock B. Acoustic overstimulation increases outer hair cell Ca2+
concentrations and causes dynamic contractions of the hearing organ. Proc Natl Acad Sci U S A
Le Prell CG, Yamashita D, Minami SB, Yamasoba T, Miller JM. Mechanisms of noise-induced hearing loss indicate multiple methods of prevention. Hear Res
Yamane H, Nakai Y, Takayama M, et al. The emergence of free radicals after acoustic trauma and strial blood flow. Acta Otolaryngol Suppl
Ohlemiller KK, Wright JS, Dugan LL. Early elevation of cochlear reactive oxygen species following noise exposure. Audiol Neurootol
Chiovenda P, Pasqualetti P, Zappasodi F, et al. Environmental noise-exposed workers: event-related potentials, neuropsychological and mood assessment. Int J Psychophysiol
Cui B, Li K, Gai Z, et al. Chronic noise exposure acts cumulatively to exacerbate Alzheimer's disease-like amyloid-β pathology and neuroinflammation in the rat hippocampus. Sci Rep
Jafari Z, Okuma M, Karem H, Mehla J, Kolb BE, Mohajerani MH. Prenatal noise stress aggravates cognitive decline and the onset and progression of beta amyloid pathology in a mouse model of Alzheimer's disease. Neurobiol Aging
Cui B, Li K. Chronic noise exposure and Alzheimer disease: is there an etiological association? Med Hypotheses
Cui B, Zhu L, She X, et al. Chronic noise exposure causes persistence of tau hyperphosphorylation and formation of NFT tau in the rat hippocampus and prefrontal cortex. Exp Neurol
Alessenko AV, Bugrova AE, Dudnik LB. Connection of lipid peroxide oxidation with the sphingomyelin pathway in the development of Alzheimer's disease. Biochem Soc Trans
Smith JV, Luo Y. Elevation of oxidative free radicals in Alzheimer's disease models can be attenuated by Ginkgo biloba extract EGb 761. J Alzheimers Dis
Sayre LM, Zagorski MG, Surewicz WK, Krafft GA, Perry G. Mechanisms of neurotoxicity associated with amyloid beta deposition and the role of free radicals in the pathogenesis of Alzheimer's disease: a critical appraisal. Chem Res Toxicol
Subramaniam R, Koppal T, Green M, et al. The free radical antioxidant vitamin E protects cortical synaptosomal membranes from amyloid beta-peptide(25-35) toxicity but not from hydroxynonenal toxicity: relevance to the free radical hypothesis of Alzheimer's disease. Neurochem Res
Bonet-Costa V, Pomatto LC, Davies KJ. The proteasome and oxidative stress in Alzheimer's disease. Antioxid Redox Signal
Janciauskiene S, Wright HT, Lindgren S. Fibrillar Alzheimer's amyloid peptide Abeta(1-42) stimulates low density lipoprotein binding and cell association, free radical production and cell cytotoxicity in PC12 cells. Neuropeptides
Butterfield DA, Lauderback CM. Lipid peroxidation and protein oxidation in Alzheimer's disease brain: potential causes and consequences involving amyloid beta-peptide-associated free radical oxidative stress. Free Radic Biol Med
Manikandan S, Padma MK, Srikumar R, Jeya Parthasarathy N, Muthuvel A, Sheela Devi R. Effects of chronic noise stress on spatial memory of rats in relation to neuronal dendritic alteration and free radical-imbalance in hippocampus and medial prefrontal cortex. Neurosci Lett
Shukla M, Roy K, Kaur C, et al. Attenuation of adverse effects of noise induced hearing loss on adult neurogenesis and memory in rats by intervention with Adenosine A(2A) receptor agonist. Brain Res Bull
Azman KF, Zakaria R, AbdAziz C, Othman Z, Al-Rahbi B. Tualang honey improves memory performance and decreases depressive-like behavior in rats exposed to loud noise stress. Noise Health
Jafari Z, Mehla J, Kolb BE, Mohajerani MH. Gestational stress augments postpartum β-amyloid pathology and cognitive decline in a mouse model of Alzheimer's disease. Cereb Cortex
Sonnen JA, Breitner JC, Lovell MA, Markesbery WR, Quinn JF, Montine TJ. Free radical-mediated damage to brain in Alzheimer's disease and its transgenic mouse models. Free Radic Biol Med
Lacerda A, Leroux T, Morata T. Ototoxic effects of carbon monoxide exposure: a review. Pro Fono
World Health Organization. Air quality guidelines for Europe. WHO Reg Publ Eur Ser
Varon J, Marik PE, Fromm RE, Jr., Gueler A. Carbon monoxide poisoning: a review for clinicians. J Emerg Med
Hullmann M, Albrecht C, van Berlo D, et al. Diesel engine exhaust accelerates plaque formation in a mouse model of Alzheimer's disease. Part Fibre Toxicol
Prockop LD. Carbon monoxide brain toxicity: clinical, magnetic resonance imaging, magnetic resonance spectroscopy, and neuropsychological effects in 9 people. J Neuroimaging
Kondziella D, Danielsen ER, Hansen K, Thomsen C, Jansen EC, Arlien-Soeborg P. 1H MR spectroscopy of gray and white matter in carbon monoxide poisoning. J Neurol
Bilski B. Interaction between noise and ototoxic agents in the work environment. Med Pr
Riego G, Redondo A, Leánez S, Pol O. Mechanism implicated in the anti-allodynic and anti-hyperalgesic effects induced by the activation of heme oxygenase 1/carbon monoxide signaling pathway in the central nervous system of mice with neuropathic pain. Biochem Pharmacol
Sekiya K, Nishihara T, Abe N, et al. Carbon monoxide poisoning-induced delayed encephalopathy accompanies decreased microglial cell numbers: Distinctive pathophysiological features from hypoxemia-induced brain damage. Brain Res
Sonnen JA, Larson EB, Gray SL, et al. Free radical damage to cerebral cortex in Alzheimer's disease, microvascular brain injury, and smoking. Ann Neurol
Paul KC, Haan M, Mayeda ER, Ritz BR. Ambient air pollution, noise, and late-life cognitive decline and dementia risk. Annu Rev Public Health
Andersson J, Oudin A, Sundström A, Forsberg B, Adolfsson R, Nordin M. Road traffic noise, air pollution, and risk of dementia - results from the Betula project. Environ Res
Chen GD, McWilliams ML, Fechter LD. Intermittent noise-induced hearing loss and the influence of carbon monoxide. Hear Res
Sheikh MA, Williams W, Connolly R. Exposure to ototoxic agents and noise in workplace –a literature review. Proceedings of ACOUSTICS 2016; 2016; Brisbane, Australia
Fechter LD, Young JS, Carlisle L. Potentiation of noise induced threshold shifts and hair cell loss by carbon monoxide. Hear Res
Peña-Bautista C, Baquero M, Vento M, Cháfer-Pericás C. Free radicals in Alzheimer's disease: Lipid peroxidation biomarkers. Clin Chim Acta
Cheignon C, Tomas M, Bonnefont-Rousselot D, Faller P, Hureau C, Collin F. Oxidative stress and the amyloid beta peptide in Alzheimer's disease. Redox Biol
Bagheri F, Rezaei M, Rashedi V. Auditory training among older adults with Alzheimer disease and central auditory processing disorder. Avicenna J Neuro Psycho Physiol
Dasuri K, Zhang L, Keller JN. Oxidative stress, neurodegeneration, and the balance of protein degradation and protein synthesis. Free Radic Biol Med
Butterfield DA, Di Domenico F, Barone E. Elevated risk of type 2 diabetes for development of Alzheimer disease: a key role for oxidative stress in brain. Biochim Biophys Acta
Herman F, Westfall S, Brathwaite J, Pasinetti GM. Suppression of presymptomatic oxidative stress and inflammation in neurodegeneration by grape-derived polyphenols. Front Pharmacol
Korolainen MA, Nyman TA, Nyyssönen P, Hartikainen ES, Pirttilä T. Multiplexed proteomic analysis of oxidation and concentrations of cerebrospinal fluid proteins in Alzheimer disease. Clin Chem
Mancuso C, Scapagini G, Curró D, et al. Mitochondrial dysfunction, free radical generation and cellular stress response in neurodegenerative disorders. Front Biosci
Recuero M, Vicente MC, Martínez-García A, et al. A free radical-generating system induces the cholesterol biosynthesis pathway: a role in Alzheimer's disease. Aging Cell
Butterfield DA, Howard BJ, LaFontaine MA. Brain oxidative stress in animal models of accelerated aging and the age-related neurodegenerative disorders, Alzheimer's disease and Huntington's disease. Curr Med Chem
Sayre LM, Smith MA, Perry G. Chemistry and biochemistry of oxidative stress in neurodegenerative disease. Curr Med Chem
Castellani RJ, Moreira PI, Liu G, et al. Iron: the Redox-active center of oxidative stress in Alzheimer disease. Neurochem Res
Yaribeygi H, Panahi Y, Javadi B, Sahebkar A. The underlying role of oxidative stress in neurodegeneration: a mechanistic review. CNS Neurol Disord Drug Targets
Guan ZZ. Cross-talk between oxidative stress and modifications of cholinergic and glutaminergic receptors in the pathogenesis of Alzheimer's disease. Acta Pharmacol Sin
Axelsen PH, Komatsu H, Murray IV. Oxidative stress and cell membranes in the pathogenesis of Alzheimer's disease. Physiology (Bethesda)
Moreira PI, Santos MS, Oliveira CR, et al. Alzheimer disease and the role of free radicals in the pathogenesis of the disease. CNS Neurol Disord Drug Targets
Baldeiras I, Santana I, Proença MT, et al. Oxidative damage and progression to Alzheimer's disease in patients with mild cognitive impairment. J Alzheimers Dis
Zafrilla P, Mulero J, Xandri JM, Santo E, Caravaca G, Morillas JM. Oxidative stress in Alzheimer patients in different stages of the disease. Curr Med Chem
Cervellati C, Cremonini E, Bosi C, et al. Systemic oxidative stress in older patients with mild cognitive impairment or late onset Alzheimer's disease. Curr Alzheimer Res
Gu F, Zhu M, Shi J, Hu Y, Zhao Z. Enhanced oxidative stress is an early event during development of Alzheimer-like pathologies in presenilin conditional knock-out mice. Neurosci Lett
Pappolla MA, Chyan YJ, Omar RA, et al. Evidence of oxidative stress and in vivo neurotoxicity of beta-amyloid in a transgenic mouse model of Alzheimer's disease: a chronic oxidative paradigm for testing antioxidant therapies in vivo. Am J Pathol
Altunoglu E, Guntas G, Erdenen F, et al. Ischemia-modified albumin and advanced oxidation protein products as potential biomarkers of protein oxidation in Alzheimer's disease. Geriatr Gerontol Int
Goschorska M, Gutowska I, Baranowska-Bosiacka I, et al. Influence of acetylcholinesterase inhibitors used in Alzheimer's disease treatment on the activity of antioxidant enzymes and the concentration of glutathione in THP-1 macrophages under fluoride-induced oxidative stress. Int J Environ Res Public Health
Moreira PI, Sayre LM, Zhu X, Nunomura A, Smith MA, Perry G. Detection and localization of markers of oxidative stress by in situ methods: application in the study of Alzheimer disease. Methods Mol Biol
Skoumalova A, Rofina J, Schwippelova Z, Gruys E, Wilhelm J. The role of free radicals in canine counterpart of senile dementia of the Alzheimer type. Exp Gerontol
Wojtunik-Kulesza KA, Oniszczuk A, Oniszczuk T, Waksmundzka-Hajnos M. The influence of common free radicals and antioxidants on development of Alzheimer's Disease. Biomed Pharmacother
Smith MA, Hirai K, Hsiao K, et al. Amyloid-beta deposition in Alzheimer transgenic mice is associated with oxidative stress. J Neurochem
Butterfield DA, Drake J, Pocernich C, Castegna A. Evidence of oxidative damage in Alzheimer's disease brain: central role for amyloid beta-peptide. Trends Mol Med
Mattson MP. Pathways towards and away from Alzheimer's disease. Nature
Khan SM, Cassarino DS, Abramova NN, et al. Alzheimer's disease cybrids replicate beta-amyloid abnormalities through cell death pathways. Ann Neurol
Perry G, Taddeo MA, Petersen RB, et al. Adventiously-bound redox active iron and copper are at the center of oxidative damage in Alzheimer disease. BioMetals
Ansari MA, Joshi G, Huang Q, et al. In vivo administration of D609 leads to protection of subsequently isolated gerbil brain mitochondria subjected to in vitro oxidative stress induced by amyloid beta-peptide and other oxidative stressors: relevance to Alzheimer's disease and other oxidative stress-related neurodegenerative disorders. Free Radic Biol Med
Santos RX, Correia SC, Zhu X, et al. Nuclear and mitochondrial DNA oxidation in Alzheimer's disease. Free Radic Res
. 2012;46: 565-576
Schipper HM. Brain iron deposition and the free radical-mitochondrial theory of ageing. Ageing Res Rev
Beal MF. Mitochondria, free radicals, and neurodegeneration. Curr Opin Neurobiol
Hashim A, Wang L, Juneja K, Ye Y, Zhao Y, Ming LJ. Vitamin B6s inhibit oxidative stress caused by Alzheimer's disease-related Cu(II)-β-amyloid complexes-cooperative action of phospho-moiety. Bioorg Med Chem Lett
Lagouge M, Larsson NG. The role of mitochondrial DNA mutations and free radicals in disease and ageing. J Intern Med
Naderi J, Lopez C, Pandey S. Chronically increased oxidative stress in fibroblasts from Alzheimer's disease patients causes early senescence and renders resistance to apoptosis by oxidative stress. Mech Ageing Dev
Gamba P, Leonarduzzi G, Tamagno E, et al. Interaction between 24-hydroxycholesterol, oxidative stress, and amyloid-β in amplifying neuronal damage in Alzheimer's disease: three partners in crime. Aging Cell
Atwood CS, Obrenovich ME, Liu T, et al. Amyloid-beta: a chameleon walking in two worlds: a review of the trophic and toxic properties of amyloid-beta. Brain Res Brain Res Rev
Aldred S, Bennett S, Mecocci P. Increased low-density lipoprotein oxidation, but not total plasma protein oxidation, in Alzheimer's disease. Clin Biochem
Turnbull S, Tabner BJ, El-Agnaf OM, Twyman LJ, Allsop D. New evidence that the Alzheimer beta-amyloid peptide does not spontaneously form free radicals: an ESR study using a series of spin-traps. Free Radic Biol Med
Korolainen MA, Pirttilä T. Cerebrospinal fluid, serum and plasma protein oxidation in Alzheimer's disease. Acta Neurol Scand
Miranda S, Opazo C, Larrondo LF, et al. The role of oxidative stress in the toxicity induced by amyloid beta-peptide in Alzheimer's disease. Prog Neurobiol
Guidi I, Galimberti D, Lonati S, et al. Oxidative imbalance in patients with mild cognitive impairment and Alzheimer's disease. Neurobiol Aging
Markesbery WR, Lovell MA. DNA oxidation in Alzheimer's disease. Antioxid Redox Signal
Praticó D. Evidence of oxidative stress in Alzheimer's disease brain and antioxidant therapy: lights and shadows. Ann N Y Acad Sci
Praticó D, Zhukareva V, Yao Y, et al. 12/15-lipoxygenase is increased in Alzheimer's disease: possible involvement in brain oxidative stress. Am J Pathol
[Figure 1], [Figure 2], [Figure 3]