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Alzheimer’s Disease
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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
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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
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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.
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Alzheimer’s Disease
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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.
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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.
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