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Alzheimer's Disease Summary

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Affinity of Cu+ for the Copper-Binding Domain of the Amyloid-β Peptide of Alzheimer's Disease Summary Alzheimer’s disease (AD) is part of a group of diseases called dementia and it is the most typical type of dementia, making up about 60-80% of total dementia types. This disease is becoming more and more prevalent as people’s lifespan increases, because of the ever-advancing medical field. Additionally, the total number of Alzheimer’s cases is expected to double over the next 20 years. Most generally, it affects people over the age of 65, but can affect people as young as the age of 40 and is the 5th leading cause of death for the elderly. Once diagnosed, a patient normally lives 1 to 10 years and in some unusual cases, up to 20 years.…show more content…
In addition to copper, iron also appears to play a key role as a metal amyloid that can form reactive oxygen species (ROS). The ROS seem to play an instrumental role in neurodegenerative effects that are seen with AD. However, it appears based on recent research that the effects that ROS have on cells can be stopped because it has been shown that Aβ quenches hydroxyl radicals. The authors of this paper have demonstrated in a previous publication that the monomeric and soluble form of the Aβ peptide will bind Cu+ in a linear bis-His geometry. This geometry is important because it is kinetically slow to react with oxygen to form ROS. As mentioned earlier, ROS are thought to be correlated with neurodegeneration that is seen in AD so if ROS were slow to form that would slow down the progression of the…show more content…
Additionally, the authors realize that the idea of the possible formation of Cu2+ Aβ species is unresolved. They hope that by finding the dissociation constant of Cu2+ Aβ, that the issue becomes partly resolved. This is because the dissociation constant plays a key role in vivo. If it is too high then it will be impossible to form Cu2+ Aβ to form in the presence of human serum albumin (HSA). HSA is found in cerebral spinal fluid. There is a strong Cu2+coordination mode, which would not allow for sustained redox cycling of Cu2+. However, if there are significant concentrations of ascorbate it may be possible. Overall, the authors conclude that monomeric Aβ binds more tightly to Cu+ than Cu2+ and that it is important to the in vivo oxidation state. Plus, they showed in an earlier study that the slowness of the Cu+ Aβ helps to slow down the production of ROS, which would slow the neurodegeneration seen in AD. Also, the amount of ascorbate that is present in extracellular fluid could generate Cu+, even though in plasma extracellular copper is thought to only be in the Cu2+ oxidation state. The authors acknowledge that this is a controversial finding and that in vivo testing would need to be done in order to verify their
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