Oxidative Stress in Alzheimer’s Disease and Mild Cognitive Impairment

Journal of Alzheimers Disease October 16, 2012 [epub] Natividad Lopez, Consuelo Tormo, Isabel De Blas, Isabel Llinares, Jordi AlomFree Radical Damage=Oxidative Stress=Reactive Oxygen Species (ROS)=LipidPeroxidation KEY POINTS FROM THIS STUDY: 1) Oxidative stress may be a decisive factor in Alzheimers disease (AD) and inthe initial phase of mild cognitive impairment (MCI). 2) This study measured blood oxidative stress using the following: A)) Levels of malondialdehyde (MDA), a marker of oxidative damage to thedouble bonds of lipids; a marker for oxidative degradation of cellular membranes. B)) Levels of superoxide dismutase (SOD), an enzymatic, endogenousantioxidant; blocks the conversion of superoxide radicals into hydrogen peroxide. C)) Levels of ceruloplasmin, another endogenous antioxidant. D)) Level of copper, a powerful pro-oxidant metal ion; a driver of free radicalproduction. 3) The study group consisted of 36 patients with AD, 18 patients with MCI, and33 healthy aged subjects. Blood samples were obtained from each subject. 4) A significantly higher copper level was found in patients with AD and MCIcompared to the control group. [Important point] 5) Levels of MDA were higher in patients from the AD and MCI groups than inthe control group. 6) Our findings support the hypothesis that oxidative stress might represent asign of AD pathology and could be an early event in the progression of MCI to AD. 7) Previous research suggests that oxidative stress may contribute to thepathogenic cascade in Alzheimers disease (AD). 8) Oxidative damage to essential biomolecules (nucleic acids, lipids, proteins, orcarbohydrates) alter the biological role that these play in physiological conditions. 9) The presence of high levels of unsaturated lipid content (that are readilyattacked by free radicals) coupled with high oxygen utilization, high level of redoxtransition metal ions, and relatively poor antioxidant systems makes the brainparticularly vulnerable to oxidative damage. 10) In the brain, due to its high lipid content, the most important mechanism inthe damage due to free radicals is the peroxidation of lipids. 2 11) Cu imbalance contributes to the oxidative stress that is part of thepathogenesis of AD and can play an important role in the development of AD. 12) Mild cognitive impairment (MCI) may be the earliest stage of AD. 13) Cu levels showed a significant increase in the serum of AD and MCI patients,compared to the control group. Cu showed a clear gradient from healthy to ADpatients passing through MCI subjects. 14) Our data show a steady increase in serum Cu levels from healthy subjects toMCI and AD patients. 15) Our findings could support the hypothesis that an increase in serum Culevels could be related to lipid peroxidation due to its correlation with MDA levels,resulting in an involvement of Cu in oxidative damage. 16) Plasma levels of MDA were significantly higher in subjects with AD and MCI, incomparison to healthy controls. 17) Previous studies reported increased oxidative damage in patients with MCI.Plasma in MCI patients is known to have lower levels of non-enzymatic antioxidants[exogenous antioxidants, like vitamin E and C] and decreased activity of antioxidantenzymes [endogenous antioxidants like superoxide dismutase, catalase, andglutathione peroxidase], increased oxidative damage in nuclear and mitochondrialDNA, and higher levels of isoprostanes compared to that of the healthy subjects. 18) The current results suggest that oxidative stress [free radical damage] maybe present in early cognitive decline. 19) In conclusion, we found that lipid peroxidation occurs in patients with MCIand AD in a similar way, suggesting that oxidative stress might represent a signalof the AD pathology and could be an early event in the progression of MCI to AD. KEY CONCEPTS FROM DAN MURPHY *The brain is primarily composed of fat, especially unsaturated fats. *The unsaturated fats of the brain are particularly vulnerable to oxidative stress(free radicle damage). This process is called lipid peroxidation. *Copper significantly accelerates lipid peroxidation (free radical damage) and istherefore a factor in accelerating mild cognitive impairment (MCI) and Alzheimersdisease. Other studies we have reviewed [AR 49-11 and 3-12] concur and indicatethat the primary source of such copper is municipal drinking water and copperfound in dietary supplements; suggesting that our municipal drinking water shouldbe reversed osmosis and our supplements should essentially be copper free. *Both exogenous and exndogenous antioxidants are important in reducing brainfree radical damage. My protocol for doing such is attached. *One should probably not consume fish oil without also increasing consumption ofantioxidants [Article Review 30-12].Supplements That Everyone Should TakeEvery Day All People(Nutri-West: 800-443-3333) 1) Vitamin D3800 IU per day for infants (1 Vitamin D 400) 2,500 IU – per day for children (1 Complete Immuno D3) 5,000 IU per day (1 Complete Hi D3) 2) Multiple Vitamin-MineralShould be copper free (less than 100 micrograms) and iron free(3 Core Level Health Reserves) 3) Omega-3 fatty acids Children: The DHA should be greater than the EPA (2.6/1) 900 mg of EPA + DHA per day (8 Complete Childrens EPA/DHA) Adults: Has an ideal ratio of ALA, EPA, DHA, and GLA; EPA should be double DHA3,000 mg of EPA + DHA per day (6 Complete Omega-3 Essentials)(or 1 teaspoon of Complete Hi-Potency Omega-3 Liquid) 4) Omega-3 antioxidants (1 Complete Omega-3 Co-Factors per gram of EPA + DHA) 5) Mitochondrial Health (adults only): A) Acetyl-l-carnitine 680 mg per day B) Alpha-lipoic acid 240 mg per day (4 Complete AG) C) CoQ 10 10 mg per day 6) Increase Glutathione A) N-Acetyl Cysteine, or NAC: (Complete Glutathione)Children 120 mg per day 2 per dayAdults 240 mg per day 4 per day B) Undenatured Whey Protein: (Complete Whey-G)Children 7 grams per day 1 scoop per dayAdults 21 grams per day 3 scoops per day 7) Resveratrol (adults only)100 mg per day(4 Complete Neuro) 8) Curcumin (Tumeric) (adults only)200 mg per day AntioxidantsExogenous EndogenousMust Come Made by ourFrom Diet DNAVitamin C SuperoxideDismutaseVitamin E CatalaseFruits GlutathionePeroxidaseVegetablesEtc.Endogenous antioxidants have anenormous advantage over exogenousantioxidants Sally Nelson, The induction of human superoxide dismutase and catalase invivo: A fundamentally new approach to antioxidant therapy, Free RadicalBiology & Medicine, 2006, from the Webb-Warning Institute for Cancer,Aging and Antioxidant Research, University of Colorado, and theDepartment of Medicine University of ColoradoATP95 %O2 + Glucose5 %Free RadicalsOxygen Free RadicalsReactive Oxygen Species(ROS)Superoxide RadicalSuperoxideDismutase H2O2 + H2OCatalase GlutathionePeroxidaseO2 + H20