Hall 1

Julia Hall

Ms. Chawkat

Period: 3

Data Collection

Data

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
http://go.galegroup.co A(beta) raises the levels of increased levels of
m/ps/i.do?p=GPS&sw 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
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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
proven more effective at reducing caused plaque
Lombardi, V. R. M.,
plaque formation in the brain and formation, but Carrera
Lakshmana, M. K., neurodegeneration than the current focused on reducing
Cacabelos, R., & CFA/IFA vaccine. Recent research the neuroinflammatory
Vigo, C. (2015). A has indicated that reaction. Carrera tested
comparative neuroinflammatory reactions have a new vaccine, EB101,
evaluation of a novel been observed around A(beta) in the hippocampal of
vaccine in APP/PS1 plaque, leading to the mice to compare its
neurodegeneration found in effectiveness to the
mouse models of
Alzheimer’s Disease. The scientists current CFA/IFA
alzheimer's disease. compared the efficacy of EB101 and vaccine. Carrera found
BioMed Research CFA/IFA in APP/PS1 mice before more plaque clearance
International. and after A(beta) pathology. The and an anti-
Retrieved from EB101 vaccine was prepared using inflammatory response
http://link.galegroup.c two milligrams of A(beta), one in the hippocampal
om/apps/doc/A458163 milliliter of water, and 0.1 milliliters mice with the EB101
of 10x PBS. Whereas, the CFA/IFA vaccine. Sell believed
378/GPS?u=glen2023 vaccine was prepared using Freund’s that an effective
3&sid=GPS&xid=747 adjuvant and incomplete Freund’s treatment could be
7ffc8 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
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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
physiological alpha-secretase, treatment for
Thines, E., ...Endres,
ADAM10, which prevents toxic Alzheimer’s disease.
K. (2015). Extract of A(beta) peptides from developing. However, Schuck
Caragana sinica as a Recent research has indicated that found that the
potential therapeutic the overexpression of the ADAM10 overexpression of
option for increasing gene has dramatically reduced ADAM10 prevented
alpha-secretase gene plaque formation and the learning the formation of the
expression. deficits found in Alzheimer’s A(beta) peptides.
disease. The scientists used extracts Schuck found that the
Phytomedicine:
of medicinal plants from Korea to C. sinica extract and
International Journal identify the alpha-secretases alpha-viniferin were
of Phytotherapy & enhancers in the ADAM10 gene. the restricting
Phytopharmacology, The extracts were then injected into components in the
22(11), 1027+. wild type mice, and four hours after ADAM10 protein. The
Retrieved from injection the mice were sacrificed to researchers now want
http://link.galegroup.c assess the effect of the injection on to combine the two
their brain tissue. The scientists extracts into one
om/apps/doc/A434222 collected their brain and liver tissue bioactive component
715/GPS?u=glen2023 and total RNA to determine the as a therapeutic option
3&sid=GPS&xid=f75 expression of ADAM10. The for Alzheimer’s
dcae4 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., Huang, Y., This clinical investigation of
Mo, D., Song, L., Jia, Alzheimer’s Disease assesses how
B., ...Miao, Z. (2016). the BACE-1 protein is related to the
Deposition of BACE-1 plaque formation in the brain.
Protein in the Brains of Recent research has indicated that
APP/PS1 Double plaque build-up in the brain is
Transgenic Mice. caused by the expression of the
BioMed Research A(beta) protein. The scientists
International. performed many tests on the wild
Retrieved from type mice to evaluate how the plaque
http://link.galegroup.co buildup was affecting their cognitive
m/apps/doc/A5207158 functions. The scientists then
15/GPS?u=avlr&sid=G harvested brain tissue from the wild
PS&xid=e1446621 type mice after six months and found
that the BACE-1 protein surrounded
the plaque formation in brain.
Therefore, the researchers hope that
by reducing the expression of the
BACE-1 protein the plaque
formation will be reduced in the
brain due to the lower levels of the
A(beta) protein. However, more
research still needs to be conducted
to conclude the results and further
study the pathology of Alzheimer's
disease, but researchers are one step
closer to finding a cure for
Alzheimer’s disease.
Hall 4
Similar to Sell, Luo
hopes that by reducing
the expression of the
BACE-1 protein the
plaque formation in the
brain could be reduced.
All the scientists agree
on needing to reduce
the levels of A(beta)
protein to reduce the
plaque formation in the
brain. However, they
all had different
approaches for how
they were going to test
their hypothesis in
mice. More research
still needs to be done
to conclude the results
of these experiments,
but based on these four
sources the most
effective protocol
would be to use
selective reduction or
RNA to discover
which proteins are
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
brain.
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Rationale

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.

Analysis

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
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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.

Conclusion

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 and vaccinations 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.

In conclusion, 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
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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 two methods, selective reduction and vaccinations,

scientists could find a cure for Alzheimer’s disease and save the lives of millions of people.