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Always Remember Those Who Cannot: A

Treatment for Alzheimer’s Disease

Julia Hall
Independent Research G/T
May 1, 2018

Advisor: Dr. Jeremiah Cohen

Alzheimer’s is a degenerative brain disease that causes the cerebral cortex and
hippocampus to shrink and plaque to develop in the brain. Often confused with the changes
associated with aging, Alzheimer’s disease is much more than just memory loss because it
causes cognitive impairment and patients start to forget who they are as a person. There is
currently no cure for Alzheimer’s disease, but there have been major discoveries in the field as
scientists attempt to discover a viable treatment protocol for Alzheimer’s disease. Scientist have
found great success by using methods of protein manipulation, vaccinations, and natural products
to treat Alzheimer’s disease. The researcher came to the conclusion that the most effective
treatment for Alzheimer’s disease would be to determine through shRNA and selective reduction
which proteins were affecting the levels of A(beta) peptides in the brain, and then to develop a
vaccine that would either target or increase the expression of these proteins. If this research could
help scientists get one step closer to discovering a cure for Alzheimer’s disease and help millions
of suffering people, then that will be the true victory.

Auguste Deter was the first patient diagnosed with Alzheimer’s disease by Dr. Alois

Alzheimer in 1901. If a patient came in today showing symptoms of Alzheimer’s disease,

doctors could not help them anymore than Dr. Alzheimer could help Auguste in 1901.

Alzheimer’s affects forty million people nationwide and there has been significant progress in

medicine with vaccines and treatments for cancer, but almost no progress with treating

Alzheimer’s disease. The lack of progress in developing an effective treatment protocol for

Alzheimer's disease is due to the fact that scientists are still trying to apprehend the pathology

of the disease, so they can better understand how to treat it. Also, Alzheimer’s research does not

receive as much as cancer research because there is a lack of Alzheimer’s awareness in the

world since it has been mistaken as a symptom of aging for many years. Out of the leading

causes of death in the world Alzheimer’s is the only one that does not have a cure or a method

to slow it down.

Alzheimer’s is a degenerative brain disorder where plaque begins to build up in the

brain causing the cerebral cortex and hippocampus to shrivel and become damaged (Cohen).

Over time, patients will experience memory loss and cognitive impairment as the disease

progresses and more plaque builds up in the brain. The disease could start with something as

simple as forgetting where the patient left their keys, to what happened the night before, to not

knowing what day or year it is, to forgetting the names of their children, and finally forgetting

who they are. If scientists combine alternative methods of manipulating protein expression,

vitamins, and vaccinations then they could be one step closer to finding an effective treatment

protocol for Alzheimer’s disease.

Literature Review
First, manipulating protein expression could be an effective treatment for Alzheimer’s

disease. For example, scientists have focused on manipulating gonadotropins by targeting

multiple pleiotropic downstream consequences (Casadesus). Reducing the expression of proteins

like gonadotropins could help reduce and prevent plaque development in the brain, delaying the

symptoms of early onset Alzheimer’s (Jia). In addition, the glutamate receptor antagonist,

memantine, has been used in the treatment of individuals with Alzheimer’s disease (Revett).

Overexpressing glutamate receptors such as memantine could help prevent plaque development

in the brain by prohibiting the formation of A(beta) peptides in the brain (Colligan).

Manipulating protein expression to reduce the formation of the toxic A(beta) peptides is the goal

of most of the research studies because A(beta) plaque formation causes the symptoms of

Alzheimer’s disease.

Additionally, using more natural methods like plant injections could help treat

Alzheimer’s disease as well. For instance, the resveratrol treatment, injecting the natural

supplement of resveratrol in to the infected areas of the brain, has reduced neuroinflammatory

reactions in the brain and could help prevent symptoms of Alzheimer's disease from developing

(Kempuraj). Physical exercise and certain vitamins have also been proven to ward off

Alzheimer’s disease (Wollen). Physical exercise can keep your brain healthier and younger,

which could delay neurodegenerative disorders like Alzheimer’s disease (Lee). Using natural

methods such as daily exercise and plant injections help keep the brain younger and reduce

inflammatory reactions in the brain. Therefore, natural products have been proven an effective

treatment for Alzheimer’s disease.

Vaccines and medication are another promising method for treating Alzheimer’s disease.

For example, the Tau aggregation inhibitor is methylthioninium which is a drug that targets
A(beta) plaque accumulation (Panza). The Tau aggregation inhibitor which has been used to treat

Diabetes, has also been found to promote plaque reduction in Alzheimer’s disease (Dovey).

Also, there is an antibody-based immunotherapeutic approach that helps prevent some of the

symptoms of Alzheimer’s disease (Sevigny). The antibody immunotherapeutic approach uses

vaccines to reduce the A(beta) toxicity levels in the brain which could be effective in treatment

protocols because it could lessen the effects of the plaque formation (Meek). Thus, vaccines and

medication would be an effective treatment method for Alzheimer’s disease because they help

diminish the toxicity levels of the A(beta) plaque formation.

Lastly, combining methods of vaccines, protein manipulation, and natural methods for an

effective Alzheimer’s treatment could be the most effective method to treat the disorder because

each method on its own has had varied success and it might be the best way to tackle the

complex disease. There has not been a lot of studies that have combined methods, but there have

been some. For example, some researchers have used extracts from plants to inject in to the brain

before they manipulated different proteins and enzymes in the brain (Kempuraj). Also, other

researchers have studied the effects of using various A(beta) vaccines and tested different protein

inhibitors such as GAMMA and BACE proteins (Jia). These researchers have found that these

methods have reduced inflammation and oxidants in the brain preventing some of the symptoms

of Alzheimer’s disease.

The three main approaches to Alzheimer’s treatment have been manipulating protein

expression, using natural methods, and vaccinations. Each methods has had some success, but it

has been limited because none of the three methods have found a way to cure or reverse the

symptoms of Alzheimer’s. Therefore, the researcher gathered data on the effectiveness of

different clinical trials to compare the results with the thesis. The sources that were analyzed
used methods of protein manipulation, plant injections, and/or vaccinations to treat Alzheimer's


Data Collection

Source: Summary: Contribution to

Question, Could
reducing the
expression of certain
proteins be an effective
treatment method for
Alzheimer’s disease?

Sell, G. L., Schaffer, This clinical investigation of The plaque formation

T. B., & Margolis, S. Alzheimer's Disease discusses a new in the brain that leads
S. (2017). Reducing treatment method where researchers to neurodegeneration
expression of synapse- have prevented the development of and cognitive
restricting protein learning and memory deficits by impairment is caused
Ephexin5 ameliorates restricting the gene expression of the by increased levels of
Alzheimer's-like protein, Ephexin5. The protein the A(beta) protein.
impairment in mice. A(beta) restricts spine growth and Recent research has
Journal of Clinical the synapse development of the brain indicated that the
Investigation, 127(5), because it reactivates the expression protein Exphen5 has
1646+. Retrieved from of Ephexin5. To confirm that contributed to A(beta) raises the levels of increased levels of
m/ps/ Ephexin5, the researchers injected A(beta). Restricting the
=w&u=glen20233&v soluble A(beta) in to the mice expression of the
=2.1&it=r&id=GALE hippocampal neurons and used protein Exphen5
%7CA493794435&asi antibodies to detect the expression of protected neurons from
d=d55c9ad0c35cbf92 Ephexin5. They concluded that Alzheimer’s related
22b6d32ff0e287e4 A(beta) causes spine loss and spine deficits,
promotes the expression of preventing the mice
Ephexin5, causing further spine from developing
degeneration. Then, the scientists learning and memory
used selective reduction and shRNA impairments.
to target and restrict the expression
of Ephexin5. The elimination of the
Ephexin5 protected the neurons
against Alzheimer’s related spine
deficits, and the learning and
memory phenotype in the mice was
rescued. Therefore, they concluded
that by lowering the levels of the
A(beta) protein the expression of
Ephexin5 was reduced, protecting
the mice from developing learning
and cognitive deficits.

Carrera, I., This clinical research study of Carrera agrees with

Etcheverria, I., Alzheimer’s Disease discusses a Sell that the increase in
Fernandez-Novoa, L., new vaccine, EB101, that has been A(beta) levels have
Lombardi, V. R. M., proven more effective at reducing caused plaque
Lakshmana, M. K., plaque formation in the brain and formation, but Carrera
Cacabelos, R., & neurodegeneration than the current focused on reducing
Vigo, C. (2015). A CFA/IFA vaccine. Recent research the neuroinflammatory
comparative has indicated that reaction. Carrera tested
evaluation of a novel neuroinflammatory reactions have a new vaccine, EB101,
vaccine in APP/PS1 been observed around A(beta) in the hippocampal of
mouse models of plaque, leading to the mice to compare its
alzheimer's disease. neurodegeneration found in effectiveness to the
BioMed Research Alzheimer’s Disease. The scientists current CFA/IFA
International. compared the efficacy of EB101 and vaccine. Carrera found
Retrieved from CFA/IFA in APP/PS1 mice before more plaque clearance
http://link.galegroup.c and after A(beta) pathology. The and an anti-
om/apps/doc/A458163 EB101 vaccine was prepared using inflammatory response
378/GPS?u=glen2023 two milligrams of A(beta), one in the hippocampal
3&sid=GPS&xid=747 milliliter of water, and 0.1 milliliters mice with the EB101
7ffc8 of 10x PBS. Whereas, the CFA/IFA vaccine. Sell believed
vaccine was prepared using Freund’s that an effective
adjuvant and incomplete Freund’s treatment could be
adjuvant. The two vaccines were selective reduction and
injected into the plaque areas of the Carrera believed that
hippocampus and cortex of six vaccination would be
month old mice to compare their more effective.
effectiveness. The hippocampal lead
was significantly reduced in EB101
immunized mice because with the
new vaccine there was sixty-four
percent plaque clearance, whereas in
the CFA/IFA vaccine there was only
nineteen percent plaque clearance.
The scientists concluded that the
EB101 vaccine boosted antibody
generation, A(beta) plaque
reduction, and anti-inflammatory
response more effectively that
CFA/IFA vaccine when given in the
early stages of Alzheimer’s Disease.
Therefore, EB101 could be a
promising new vaccine to treat
Alzheimer’s patients, but further
studies still need to be done to
conclude the results.

Schuck, F., Schmitt, This clinical investigation of Similar to Sell, Schuck

U., Reinhardt, S., Alzheimer’s Disease discusses an targeted certain
Freese, C., Lee, I.-S., alternative approach to target the proteins when a
Thines, E., ...Endres, physiological alpha-secretase, treatment for
K. (2015). Extract of ADAM10, which prevents toxic Alzheimer’s disease.
Caragana sinica as a A(beta) peptides from developing. However, Schuck
potential therapeutic Recent research has indicated that found that the
option for increasing the overexpression of the ADAM10 overexpression of
alpha-secretase gene gene has dramatically reduced ADAM10 prevented
expression. plaque formation and the learning the formation of the
Phytomedicine: deficits found in Alzheimer’s A(beta) peptides.
International Journal disease. The scientists used extracts Schuck found that the
of Phytotherapy & of medicinal plants from Korea to C. sinica extract and
Phytopharmacology, identify the alpha-secretases alpha-viniferin were
22(11), 1027+. enhancers in the ADAM10 gene. the restricting
Retrieved from The extracts were then injected into components in the
http://link.galegroup.c wild type mice, and four hours after ADAM10 protein. The
om/apps/doc/A434222 injection the mice were sacrificed to researchers now want
715/GPS?u=glen2023 assess the effect of the injection on to combine the two
3&sid=GPS&xid=f75 their brain tissue. The scientists extracts into one
dcae4 collected their brain and liver tissue bioactive component
and total RNA to determine the as a therapeutic option
expression of ADAM10. The for Alzheimer’s
scientists then discovered that C. treatment, similar to
sinica extract and alpha-viniferin Carrera’s idea about a
were the active components in the vaccination.
ADAM10 gene that were preventing
the formation of the A(beta)
peptides. C. sinica extract and alpha-
viniferin dramatically reduced the
plaque formation and learning
deficits in the brain because they
increased the expression of the
ADAM10 gene, strengthening the
blood barrier. Researchers now want
to combine C. sinica extract and
alpha-viniferin into one bioactive
component in hopes that it could
become an ideal therapeutic option
to treat Alzheimer’s disease.
Therefore, the C. sinica extract and
alpha-viniferin bioactive component
could become an effective
therapeutic method to treat
Alzheimer’s disease, but more
research still needs to be done to
conclude the results.

Luo, G., Xu, H., This clinical investigation of Similar to Sell, Luo
Huang, Y., Mo, D., Alzheimer’s Disease assesses how hopes that by reducing
Song, L., Jia, B., the BACE-1 protein is related to the the expression of the
...Miao, Z. (2016). plaque formation in the brain. BACE-1 protein the
Deposition of BACE-1 Recent research has indicated that plaque formation in the
Protein in the Brains of plaque build-up in the brain is brain could be reduced.
APP/PS1 Double caused by the expression of the All the scientists agree
Transgenic Mice. A(beta) protein. The scientists on needing to reduce
BioMed Research performed many tests on the wild the levels of A(beta)
International. type mice to evaluate how the plaque protein to reduce the
Retrieved from buildup was affecting their cognitive plaque formation in the functions. The scientists then brain. However, they
m/apps/doc/A5207158 harvested brain tissue from the wild all had different
15/GPS?u=avlr&sid=G type mice after six months and found approaches for how
PS&xid=e1446621 that the BACE-1 protein surrounded they were going to test
the plaque formation in brain. their hypothesis in
Therefore, the researchers hope that mice. More research
by reducing the expression of the still needs to be done
BACE-1 protein the plaque to conclude the results
formation will be reduced in the of these experiments,
brain due to the lower levels of the but based on these four
A(beta) protein. However, more sources the most
research still needs to be conducted effective protocol
to conclude the results and further would be to use
study the pathology of Alzheimer's selective reduction or
disease, but researchers are one step RNA to discover
closer to finding a cure for which proteins are
Alzheimer’s disease. affecting the levels of
A(beta) peptides and
then develop a
therapeutic vaccine to
eliminate or
overexpress certain
proteins to reduce the
inflammation and
plaque formation in the

The researcher chose meta-analysis for their data collection method because they were

conducting scientific research and were not able to perform an authentic experiment. The

researcher is interested in studying the pathology of Alzheimer’s disease, and wanted to further

investigate possible treatment protocols for the disease. The researcher could not conduct an

experiment or observational study because they did not have access to mice or Alzheimer's

patients. In addition, since most Alzheimer's treatments are still in their developmental stages

analyzing academic journals seemed to be a more effective method to study the pathology of the

disease. The first academic journal that was analyzed by the researcher became the cornerstone

of their research because they were intrigued by how the scientists used selective reduction to

prevent learning deficits in mice. Therefore, the researcher looked for three sources with

experiments that tested different vaccines and methods of manipulating protein expression in the

hippocampus of mice to prevent plaque formation in the brain.


After analyzing the four academic sources, the researcher came to the conclusion that the

most effective treatment for Alzheimer’s disease would be to determine through shRNA and

selective reduction which proteins were affecting the levels of A(beta) peptides in the brain, and

then to develop a vaccine that would either target or increase the expression of these proteins.

The hypothesis is by either targeting the proteins that increase the levels of A(beta) peptides or

overexpressing the proteins that decrease the levels of A(beta) proteins so the plaque formation

and inflammation in the brain will be reduced, protecting patients from developing the learning

and memory deficits related to Alzheimer’s disease. However, more research still needs to be

conducted to formulate a more specific hypothesis. These results were not surprising because

Alzheimer’s disease was often associated as a symptom of aging and therefore did not receive as
much research funding as cancer. Therefore, scientists are just now making strides to understand

the disease, and have concluded that Alzheimer’s is a very complex disease that is difficult to

treat because it is caused by both genetic and environmental factors. Furthermore, the conclusion

of this study is very vague because scientists have acknowledged that there is still a lot about

Alzheimer’s disease that is unknown, and everyone has a different idea about how to treat

Alzheimer’s disease.


The researcher formed a conclusion that combined different ideas from scientists across

the world in attempt to answer their research question. The hope is by combining alternative

methods of manipulating protein expression, vaccinations, and natural products that scientists are

one step closer to finding an effective treatment protocol for Alzheimer’s disease. Some of the

limitations of these studies were that all four sources tested their treatments on mice and there is

yet to be an ideal mice model for the human pathology. In addition, there are a lot of immune

and age-dependent effects of Alzheimer’s disease which makes it difficult to determine if these

clinical treatments will help treat all Alzheimer’s patients. However, even though mice pathology

is not exactly like human pathology, they are close enough to come to accurate conclusions about

the effectiveness of treatments. Additionally, even if due to different environmental factors the

clinical treatments do not help everyone, if one person could be cured of Alzheimer’s disease

then that would be a victory in itself because that patient would have gotten another chance to

live their life.

These results could give hope to future researchers and patients suffering from

Alzheimer’s disease because it shows that scientists are starting to determine the cause of plaque

formation in the brain and are currently working on finding a treatment to reduce plaque buildup.
Most scientists agree that plaque formation in the brain is an effect of the increase in the A(beta)

peptide levels, and that plaque buildup causes neurodegeneration and cognitive impairment in

the brain. Therefore, in attempt to find a cure for Alzheimer’s disease scientists found that by

targeting the proteins that increase the levels of A(beta) peptides or overexpressing the proteins

that protect against the formation of A(beta) peptides plaque formation in the brain can be

reduced. Additionally, scientists used vaccines to decrease inflammation in the brain to prevent

the learning and memory deficits associated with Alzheimer’s disease. Furthermore, the

researcher concluded that by combining these three methods, selective reduction, vaccinations,

and natural products, scientists could find a cure for Alzheimer’s disease and save the lives of

millions of people.

There are 5.4 million people currently living with Alzheimer’s and for every new person

diagnosed with the disease they have about the same chance of survival as Auguste Deter did in

1901. Most people know that the pink ribbon represents Breast Cancer, but not everyone knows

that that the purple ribbon represents Alzheimer’s disease. Therefore, the goal is to raise

awareness about Alzheimer’s disease as scientists work to find a cure for this complex disease,

and even if one life could be saved from Alzheimer’s disease in the future then true progress will

have been made. There have been recent progress made in treatments, but its still in the

developmental stages. Alzheimer’s does not get the attention and support like Breast Cancer,

help support the cause, demand a cure, and always remember those who cannot.
Carrera, I., Etcheverria, I., Fernandez-Novoa, L., Lombardi, V. R. M., Lakshmana, M. K.,
Cacabelos, R., & Vigo, C. (2015). A comparative evaluation of a novel vaccine in
APP/PS1 mouse models of alzheimer's disease. BioMed Research International.
Retrieved from
Casadesus, G., Puig, E. R., Webber, K. M., Atwood, C. S., Escuer, M. C., Bowen, R. L.,
...Smith, M. A. (2006). Targeting gonadotropins: an alternative option for Alzheimer
disease treatment. Journal of Biomedicine and Biotechnology. Retrieved from
Chan, G., White, C. C., Winn, P. A., Cimpean, M., Replogle, J. M., Glick, L. R., ...De
Jager, P. L. (2015). CD33 modulates TREM2: convergence of Alzheimer loci. Nature
Neuroscience, 18(11), 1556+. Retrieved from
Colligan, Peter B., and Colin K. Combs. "Cox-2 activity is required for AB-dependent
neuronal toxicity. (Collegiate Communications--Undergraduate)." Proceedings of the
North Dakota Academy of Science, 2001, p. 41. Science In Context,
fdc0. Accessed 26 Mar. 2018.
Dovey, D. (2018, January 19). Diabetes Drug Reverses Alzheimer's Symptoms in Mice;
Reduces Brain Plaque Buildup and Improves Memory; A drug originally designed to
treat diabetes has reversed Alzheimer's disease symptoms in lab mice. Newsweek, 170(3).
Retrieved from
Gandy, S. (2011). Prevention is better than cure: attempts to reduce amyloid-[beta] in the
brain have yet to show clinical benefits. Starting treatment early is the best hope. Nature,
475(7355), S15. Retrieved from
Jia, Q., Deng, Y., & Qing, H. (2014). Potential therapeutic strategies for Alzheimer's
disease targeting or beyond [beta]-amyloid: insights from clinical trials. BioMed
Research International. Retrieved from
Kempuraj, D., Selvakumar, G. P., Thangavel, R., Ahmed, M. E., Zaheer, S., Raikwar, S.
P., ...Zaheer, A. (2017). Mast Cell Activation in Brain Injury, Stress, and Post-traumatic
Stress Disorder and Alzheimer's Disease Pathogenesis. Frontiers in Neuroscience.
Retrieved from
Lee, H. S., Park, S. W., & Park, Y. J. (2016). Effects of Physical Activity Programs on
the Improvement of Dementia Symptom: A Meta-Analysis. BioMed Research
International. Retrieved from
Luo, G., Xu, H., Huang, Y., Mo, D., Song, L., Jia, B., ...Miao, Z. (2016). Deposition of
BACE-1 Protein in the Brains of APP/PS1 Double Transgenic Mice. BioMed Research
International. Retrieved from
Ma, T., Tan, M.-S., Yu, J.-T., & Tan, L. (2014). Resveratrol as a therapeutic agent for
Alzheimer's disease. BioMed Research International. Retrieved from
Meek, A. R., Simms, G. A., & Weaver, D. F. (2013). Searching for an endogenous anti-
Alzheimer molecule: identifying small molecules in the brain that slow Alzheimer
disease progression by inhibition of [beta]-amyloid aggregation. Journal of Psychiatry
and Neuroscience, 38(4), 269+. Retrieved from
Panza, F., Solfrizzi, V., Seripa, D., Imbimbo, B. P., Lozupone, M., Santamato, A.,
...Logroscino, G. (2016). Tau-Centric Targets and Drugs in Clinical Development for the
Treatment of Alzheimer's Disease. BioMed Research International. Retrieved from
Revett, T. J., Baker, G. B., Jhamandas, J., & Kar, S. (2013). Glutamate system, amyloid
[beta] peptides and tau protein: functional interrelationships and relevance to Alzheimer
disease pathology. Journal of Psychiatry and Neuroscience, 38(1), 6+. Retrieved from
Schuck, F., Schmitt, U., Reinhardt, S., Freese, C., Lee, I.-S., Thines, E., ...Endres, K.
(2015). Extract of Caragana sinica as a potential therapeutic option for increasing alpha-
secretase gene expression. Phytomedicine: International Journal of Phytotherapy &
Phytopharmacology, 22(11), 1027+. Retrieved from
Sell, G. L., Schaffer, T. B., & Margolis, S. S. (2017). Reducing expression of synapse-
restricting protein Ephexin5 ameliorates Alzheimer's-like impairment in mice. Journal of
Clinical Investigation, 127(5), 1646+. Retrieved from
Sevigny, J., Chiao, P., Bussire, T., Weinreb, P. H., Williams, L., Maier, M., ...Sandrock,
A. (2016). The antibody aducanumab reduces A plaques in Alzheimer's disease. Nature,
537(7618), 50+. Retrieved from
Tabar, P. (2017, Summer). Untangling ALZHEIMER'S Research: Why is dementia
research so difficult? Why don't we have a cure yet? i Advance Senior Care, 66(3), 21+.
Retrieved from
Wollen, K. A. (2010, September). Alzheimer's disease: the pros and cons of
pharmaceutical, nutritional, botanical, and stimulatory therapies, with a discussion of
treatment strategies from the perspective of patients and practitioners. Alternative
Medicine Review, 15(3), 223+. Retrieved from