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Alzheimer’s Disease 1 Progress Toward a Cure for Alzheimer’s Disease “Memory is a way of holding on to the things you love, the things you are, the things you never want to lose.” (Arnold, 2005, p. 1). Imagine not being able to remember significant aspects of life, and the cause is a disease that destroys parts of the mind, corrupting memory and resulting in dementia. Known as Alzheimer’s, this illness, which was discovered in 1906 by German physician Alois Alzheimer, effects more and more people every year. Currently, more than five million Americans suffer from Alzheimer’s (Alzheimer’s Association, 2007). The prevalence rate increases significantly with age with 5% of the population over 65 suffering from the disease. Moreover, 50% of seniors who reach the age of 85 will develop Alzheimer’s (Miller, 2000). Worst of all, there is no cure. However, the race is on and great progress has been made in an attempt to terminate the despair and fatality of those facing Alzheimer’s. Alzheimer’s Disease targets the hippocampus, the area of the brain responsible for memory. This region will change shape and lose volume (Wang, 2003). Looking closer at the hippocampus, scientists have uncovered two main hallmarks of Alzheimer’s disease. The first are Amyloid Plaques, which appear between neurons as deposits of a sticky protein known as amyloid precursor protein (APP), a cell surface protein in neurons. After Amyloid beta is the protein that results from the cleavage of the natural protein, APP, the protein ends up as amyloid beta (Baringa, 1999). The second are neurofibrillary tangles, which are composed of mutated forms of related proteins called tau proteins that are conversely situated inside neurons in the appearance of twisted nerve cell fibers. Although scientists don’t yet know the function of plaques or tangles, their correlation with the disease is certain. This led LaFerla et al. (2006) to try and use antibodies to Alzheimer’s Disease 2 obliterate plaques and tangles. Antibodies are proteins normally used by the immune system to identify and neutralize foreign objects by specifically binding to them. LaFerla carried out his study by injecting tailor-made antibodies designed to bind amyloid beta into mice that were genetically engineered to make excess amyloid plaques and tau protein. These injected antibodies wiped out the plaques and the accumulated tau in the neurons that had not yet become tangles. This demonstrated that by eliminating amyloid beta, one could prevent the formation of tangles as well. Thus, the two are somehow related. In a follow-up study, the antibodies were injected into mice with preformed neurofibrillary tangles. In this case, treatment had no observable affect suggesting that once the tangles have formed, they cannot be reversed through elimination of amyloid beta. These results indicate that an anti-amyloid beta antibody injection might be successful at treating Alzheimer’s if patients are treated in the very early stages, before the formation of neurofibrillary tangles. However, diagnosing patients at such an early stage of the disease is difficult since symptoms are hard to identify. Regardless, companies are still trying to develop such treatments in hopes that new methods for early detection of Alzheimer’s will arise (Beckman, 2004). Although the formation of amyloid plaques and neurofibrillary tangles are the major trademarks of Alzheimer’s Disease, studies have shown that the disease may begin to develop long before the synthesis of these structures. Recent data suggests that Alzheimer’s is triggered when certain adult neurons, for yet unknown reasons, attempt to divide prior to their death. This was discovered in an experiment where the brains of mice affected by Alzheimer’s were compared to the brains of normal mice. In the mice with Alzheimer’s, cell cycle-related proteins were found in the neurons six months prior Alzheimer’s Disease 3 to formation of amyloid plaques and neurofibrillary tangles. It was found that the region of the brain affected by the abnormal neuronal cell division were the same region affected in Alzheimer’s patients including the hippocampus. The researchers who made this discovery are now trying to determine if ibuprofen, an anti-inflammatory drug, can be used to stop the abnormal cell cycling in neurons by inhibiting inflammation in the brain and thus possibly preventing Alzheimer’s (Yang et al., 2005). Recently, the marine invertebrate-made toxin anabaseine (DXMB) has shown to be a promising drug candidate for the treatment of Alzheimer’s. The strategy of this drug is similar to the other treatments mentioned where Alzheimer’s is attacked before the formation of amyloid plaques and neurofibrillary tangles. Anabaseine was found to demonstrate both neuroprotective activity on neurons vulnerable to beta-amyloid proteins and to stimulate levels of alpha-7 nicotinic receptors, which are highly expressed in the hippocampus where beta-amyloid is located. Research has suggested that alpha-7 receptors facilitate the cellular internalization of beta-amyloid proteins (Bourin, 2000). Therefore anabaseine functions by increasing the levels of alpha-7 nicotinic receptors to help cellular internalization. When anabaseine is slightly modified to a form known as DXMB-A and applied to a variety of animals such as mice, monkeys, rats and rabbits, different cognitive behaviors were further enhanced. Also, cells that are susceptible to the formation of amyloid beta are protected. (Kem, 2000). Therefore, with the synthesis of this new drug proves to be a promising treatment, and hopefully DXMB-A will be used on Alzheimer’s patients. There have been significant advancements toward a better understanding of the underlying mechanisms of Alzheimer’s Disease, which has led to new and innovative Alzheimer’s Disease methods of treatment. The promising antibiotic injections to eliminate amyloid plaques and pre-formed tangles, the possible use of ibuprofen to prevent abnormal cell cycling, and the use of DXMB-A to protect neuronal cells, all demonstrate the advancements being made toward a future with a cure. However, by further understanding the disease, new treatments and possibly a cure might be found. Thus, with more basic research, hopefully new remedies for Alzheimer’s Disease will be created. 4 Alzheimer’s Disease 5 References Arnold, K. (2005). Think Exist. Received October 24, 2007, from http://thinkexist.com/ quotations/memory. Alzheimer’s Association. (2007). What is Alzheimer’s? Retreived October 16, 2007, from http://www.alz.org/alzheimers_disease_what_is alzheimers.asp. Barinaga, M. (1999). An Immunization Against Alzheimer’s. Science, 285, 175. Beckman, M. (2004). Untangling Alzheimer's by paring plaques bolsters amyloid theory. Science, 305, 762. Bourin, M. (2000). Nicotinic receptors and Alzheimer's disease. Current Medical Research and Opinion, 19, 169-177. Kem, W.R. (2000). The brain alpha7 nicotinic receptor may be an important therapeutic target for the treatment of Alzheimer's disease: studies with DMXBA (GTS-21). Behavioral Brain Research, 113, 169-181. Laferla F., Salvatore O., Billings L., Kesslak P., & Cribbs D. (2006).Temporal profile of Aβ oligomerization in an in vivo model of Alzheimer’s Disease: A link between Aβ and tau pathology. JBC, 281, 1599-1604. Miller, J. (2000). Alzheimer’s Disease. Retreived December 12, 2007, from http://www.athealth.com/consumer/disorders/alzheimers.html. Wang L, Swank J.S., Glick I.E., Gado M.H., Miller M.I., Morris J.C., & Csernansky J.G. (2003). Changes in hippocampal volume and shape across time distinguish dementia of the Alzheimer type from healthy aging. NeuroImage, 2, 667-682. Alzheimer’s Disease Yang, Y., Varvel N.H., Lamb B.T., & Herrup K. (2005). Study Links Alzheimer’s Disease to Abnormal Cell Division. The Journal of Neuroscience, 26, 775-784. 6