The introduction had information that was not relevant so after the results the extra
information was deleted. The second paragraph was deleted. The third paragraph was re-written
with a focus on the amyloid plaques. The fourth paragraph was rewritten to focus on the type of
mice selected and why they were a good choice for this experiment. The conclusion was
rewritten to better tie in together the original focus of the experiment and was adjusted to
acknowledge the limitations of science.
The title of the article that was chosen is “Ethanol exposure alters Alzheimer’s-related
pathology, behavior, and metabolism in APP/PS1 mice.” This study looks into the effects of
alcohol use disorder and how it is a risk factor for developing Alzheimer's disease. The study
took place over a 10 week period where the mice were given a moderate amount of alcohol. This
was done to observe how the increased exposure to ethanol affected the mice amyloid related
functions such as pathology, metabolism, and behavior. The study used mice that were
genetically modified to show increased Alzheimer's disease symptoms such as brain cell death
and an increased number in plaque build up. The mice were divided into two groups, where one
was given water with ethanol and the other was given just water. The mice that were exposed to
ethanol displayed an increase in both cell death and plaque build up. It was found that the ethanol
had led to the alteration of size and location of the plaques in specific areas of the brain. The
mice that were given ethanol also showed abnormal behavior such as struggling with nest
building and an increase in activity level. The diet of the mice was also affected, showing
ineffective glucose tolerance and regulation. A sampling of brain fluid through tests showed that
acute ethanol consumption directly affected glucose levels in the hippocampus and selectively
increased the levels of Aβ40(which is a specific form of amyloid) during withdrawal. Ethanol
exposure altered the expression of certain receptors in the brain caused by an imbalance in
excitatory and inhibitory signaling.
Ethanol exposure to Alzheimer's patients is a complicated process. Many people are at
risk of developing Alzheimer's disease. This is a very scary realization for a lot of people. This is
seen with many people who have been affected or know someone who has been affected.
Ethanol which is what makes up alcohol has been found to alter many aspects of Alzheimer's
disease related to the complications affecting the patient. In order to understand Alzheimer's
disease and the alcohol's effect that it has, Alzheimer's disease itself needs to be understood.
Exactly what causes Alzheimer's disease is very hard to identify as the brain is very complex.
Alzheimer's disease is a disease that affects the brain and more importantly memory. It
develops as people age and recent memories begin to fade. Imagine a bookshelf with your most
recent memories being books on the top shelf and your oldest memories being on the bottom
shelf. As you get older and develop Alzheimer’s you begin to lose the most recent books on the
top shelf. These books are your most recent memories and as the disease progresses you lose
those memories. Alzeimers disease is preceded by brain injury because the damage leads to
neurodegeneration and cell death. Essentially the brain begins to break down like a car that has
100,000 miles. A characteristic of the disease is the development of amyloid deposition.
Amyloid proteins are mainly made up of amyloid beta peptides. Amyloid proteins themselves are
not the cause of Alzheimer's disease as researchers speculate that they bind on cell surfaces to
help each other attach. However, this protein can be found on cells as an aggregate species or
deposited on a variety of tissues. This leads to the development of amyloid plaque build up. The
protein possesses a distinctive β-sheet-rich fibrillar ultrastructure which evidence has suggested
has a high binding affinity for nucleic acids. The interaction with nucleic acids induces notable
changes in the conformation of amyloid proteins. Additionally, other factors such as oxidative
stress affect the regulation of amyloid proteins. Researchers theorize that amyloid plaque builds
up as a result of the misfolding of the beta sheets that make up the protein, which could be
brought on by possible factors previously mentioned. The high levels of amyloid plaque
deposition in parts of the brain are what cause cognitive impairment and Alzheimer's disease
The development of these amyloid proteins is brought on by many things, when two
genes are combined the plaque over develops. These two genes are mutant presenilin 1 and
amyloid precursor proteins (APP/PS1). These genes cause the expression of amyloid deposition
to increase.
When researching Alzheimer's disease researchers prefer to use mice. Mice are a
good research model as they are anatomically, physiologically, and genetically similar to
humans. They provide other advantages to researchers such as their small size, short life cycle,
and abundant genetic material. An issue with mice being used as the research model is that mice
don't possess the actual disease. But they merely are used to mimic physiological conditions and
typically only exhibit the amyloid buildup that is characteristic of Alzheimer's disease. The
specific type of mice that were chosen for the study were mice that possessed mutant presenilin 1
and amyloid precursor proteins (APP/PS1). These mice were chosen because they have a subset
of genes which causes the overproduction of the total accumulation of amyloid β peptides.
Cognitive impairment was observed through the mice’s abnormal behaviors and patterns. The
mice provided the researchers with a good model that allowed for an accelerated view of protein
accumulation.
To better picture the role of APP/PS1 think of a piece of cheese that is most likely to
grow mold. This mold is going to grow and spread, if it is in the fridge it will develop much
more slowly. Now imagine that this cheese was forgotten about on the counter. Being exposed
would lead to mold growing much more quickly. This is the same way that the amyloid plaque
deposition is increased in the brain; it similarly begins to spread over the brain more quickly in
varying locations. Ethanol was given to mice that expressed these genes in order to better
observe its effects. The ethanol resulted in more damage being done to the brain. This was
observed through the mice’s abnormal behaviors and patterns. The use of alcohol correlating to
increased deposition of amyloid plaque can be better explained circling back to the analogy. If
the cheese was left out in a room which was much hotter; the heat would further cause the mold
to develop. Just as the plaque continues to increasingly develop throughout the brain with the
addition of ethanol. ¶
In conclusion, be mindful of alcohol exposure as it could lead to potentially harmful
consequences later on in life. , it is best to avoid alcohol as it has been seen This is seen
throughout the study as ethanol exposure that the use of alcohol is shown to leadto leads to an
increased risk of developing Alzheimer'sof Alzheimer's diseasedisease developingment. Amyloid
plaque deposits were best observed on genetically modified mice that were studied to observe the
effects of alcohol on increasing accumulation in parts of the brain. Several limitations were
present due to the ethical concerns of using human models. Further research is needed to identify
what specific factors lead to protein malfunction as well as what genes are directly affected by
ethanol exposure. A look into what specific genes should be considered to identify exactly what
genes alcohol is damaging. Further research will need to be conducted to identify the link
between brain injury and what leads to the development of APP/PS1 genes. In order to identify
the link between alcohol and brain injury in the development of Alzehimer’s. In a society that
glorifies having the occasional drink be mindful of the long term damage that can come of these
decisions.
Sources
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on beta-amyloid plaque deposition, inflammation and synapses in the APP/PS1 mouse model of
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● Allowed for the understanding of how neural damage affected plaque build up
● Showed how brain injury lead to the development of inflammation and a decrease in
synapses that occurred
Borchelt DR, Ratovitski T, van Lare J, et al. Accelerated amyloid deposition in the brains of
transgenic mice coexpressing mutant presenilin 1 and amyloid precursor proteins. Neuron.
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● Explained how a combination of expressing certain genes lead to an acceleration in
deposition in the brain
● Helped better understand the relationship between MP1/APP
Moechars D, Lorent K, Van Leuven F. Premature death in transgenic mice that overexpress a
mutant amyloid precursor protein is preceded by severe neurodegeneration and apoptosis.
Neuroscience. 1999;91(3):819-830. doi:10.1016/s0306-4522(98)00599-5
● Detailed what lead to the mutation of certain proteins
● Explained how the neurodegeneration is what contributed to the amyloid precursor
protein