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 Alom Free Radical Damage=Oxidative Stress=Reactive Oxygen Species (ROS)=Lipid Peroxidation KEY POINTS FROM THIS STUDY: 1) Oxidative stress may be a decisive factor in Alzheimers disease (AD) and in the 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 the double bonds of lipids; a marker for oxidative degradation of cellular membranes. B)) Levels of superoxide dismutase (SOD), an enzymatic, endogenous antioxidant; 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 radical production. 3) The study group consisted of 36 patients with AD, 18 patients with MCI, and 33 healthy aged subjects. Blood samples were obtained from each subject. 4) A significantly higher copper level was found in patients with AD and MCI compared to the control group. [Important point] 5) Levels of MDA were higher in patients from the AD and MCI groups than in the control group. 6) Our findings support the hypothesis that oxidative stress might represent a sign 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 the pathogenic cascade in Alzheimers disease (AD). 8) Oxidative damage to essential biomolecules (nucleic acids, lipids, proteins, or carbohydrates) alter the biological role that these play in physiological conditions. 9) The presence of high levels of unsaturated lipid content (that are readily attacked by free radicals) coupled with high oxygen utilization, high level of redox transition metal ions, and relatively poor antioxidant systems makes the brain particularly vulnerable to oxidative damage. 10) In the brain, due to its high lipid content, the most important mechanism in the damage due to free radicals is the peroxidation of lipids. 11) Cu imbalance contributes to the oxidative stress that is part of the pathogenesis 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 AD patients passing through MCI subjects. 14) Our data show a steady increase in serum Cu levels from healthy subjects to MCI and AD patients. 15) Our findings could support the hypothesis that an increase in serum Cu levels 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, in comparison 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 antioxidant enzymes [endogenous antioxidants like superoxide dismutase, catalase, and glutathione peroxidase], increased oxidative damage in nuclear and mitochondrial DNA, and higher levels of isoprostanes compared to that of the healthy subjects. 18) The current results suggest that oxidative stress [free radical damage] may be present in early cognitive decline. 19) In conclusion, we found that lipid peroxidation occurs in patients with MCI and AD in a similar way, suggesting that oxidative stress might represent a signal of 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 is therefore a factor in accelerating mild cognitive impairment (MCI) and Alzheimers disease. Other studies we have reviewed [AR 49-11 and 3-12] concur and indicate that the primary source of such copper is municipal drinking water and copper found in dietary supplements; suggesting that our municipal drinking water should be reversed osmosis and our supplements should essentially be copper free. *Both exogenous and exndogenous antioxidants are important in reducing brain free radical damage. My protocol for doing such is attached. *One should probably not consume fish oil without also increasing consumption of antioxidants [Article Review 30-12].