Zach Anderson
Biology 113-001
22 September 2014
The Relationship Between Mitochondrial Dysfunction and Alzheimer’s Disease
There is a copious amount of scientific evidence to support the hypothesis that
Alzheimer’s disease and mitochondrial dysfunction are related. Alzheimer’s disease is
the most common cause of dementia, which causes the brain to slowly degrade over
time. Those who are affected by it gradually lose cognitive abilities as well as selfawareness and the ability to complete every day tasks such as using silverware and
getting dressed. As aforementioned, Alzheimer’s and mitochondrial dysfunction are
often mentioned together because the oxidative damage to mitochondria is quite
possibly one of the causes for the on-set and progression of Alzheimer’s disease.
Mitochondria are considered to be a target for oxidative damage as well as a
source of reactive oxygen. Oxidative damage or oxidative stress to the mitochondria
occurs when the number of groups of atoms with an uneven charge, also called free
radicals, outweighs the number of antioxidants, which counteract the free radicals. The
build-up of oxidative damage gets progressively worse as age increases. As this
process continues, mitochondria experience a decrease in the functionality of the
electron transport chain. The electron transport chain is a cell’s primary manufacturer of
Adenosine Triphosphate (ATP), which can then be broken into Adenosine Diphosphate,
causing the release of energy. Therefore, as oxidative damage to the mitochondria gets
worse, and the electron transport chain yields less ATP, the overall energy of cells
begins to decrease.
One argument for the main cause of Alzheimer’s disease is that it is caused as a
result of the lack of energy produced by mitochondria inside cells. Cells without energy
cannot properly carry out their duties and neurons in the brain begin to lose the ability to
communicate with one another via neurotransmitters. Metaphorically speaking, if a cell
affected by Alzheimer’s disease was a car, the mitochondria of the cell would be the gas
tank and it would be leaking fuel. When the mitochondria lose their ability to produce
energy (ATP) everything falls apart.
Others believe that the main cause for Alzheimer’s disease has nothing to do
with mitochondrial dysfunction but instead is the result of a genetic mutation. It seems
however possible that mitochondrial dysfunction can be the result of a genetic mutation,
which could just be one contributing factor among many that result in the horrible form
of dementia that is Alzheimer’s disease.
Because of its slowly developing nature and its lack of a cure, Alzheimer’s
disease is one of the most emotionally taxing diseases to have to watch a loved one
experience. In the later stages of Alzheimer’s disease, some patients don’t even have
the motor skills to chew and swallow food and have such a low cognitive ability that they
will forget things like their own birthday and even their own name. A consistently
successful treatment option has yet to be discovered for Alzheimer’s disease but as
technological advancements are made, scientists are developing new theories as to
how it can be cured. For example thanks to the human genome project, discoveries
have been made in regards to genetic mutations that may play a role in the
development of Alzheimer’s disease as well as other mitochondrial disorders. Rudolph
Tanzi and Lars Bertram wrote that several mutations along three different genes (APP,
PSEN1, and PSEN2) have been deemed the possible cause of the early-onset of the
disease and a polymorphism in the Apolipoprotein E gene has been discovered to be
associated with the late onset of Alzheimer’s disease. They also go on to say however
that the genes aforementioned only account for close to thirty percent of the genetic
variance for Alzheimer’s disease. This means that the genetic factors that cause the
disease are still not fully understood.
Once more information is collected on the mutations of specific genes that cause
mitochondria to experience oxidative damage; gene therapy may be a possible method
for curing Alzheimer’s disease and many other mitochondrial disorders. Gene therapy
is essentially the use of a viral vector to make a slight change to someone’s DNA. If
doctors knew which sequence of DNA was responsible for the occurrence of oxidative
damage they could replace that sequence using an appropriate viral vector with the
sequence that does not contain a mutation. This process however has many
limitations. For starters, the improper use of viral vectors can cause significant harm to
the patient it is being used on. If the virus inserts the DNA into the wrong place, serious
defects can come about. This means that there is absolutely no room for error making it
hard to advance this technology further. Also, some viruses can change their genomes
so even if the correct sequence of DNA is inserted into the virus it can be changed if the
vector is not stable. Another potential problem with gene therapy is that in some cases
it has to be able to target specific types of cells. This type of treatment has a long way
to go before it is perfected but it definitely has potential to be a great success.
One problem that hinders the progress of gene therapy technology is the ethical
issue it presents. Is it ethical to attempt to rid a patient of Alzheimer’s disease through
the use of gene therapy when the cost of failure could be another illness or defect that
could even be fatal? One would have to do some serious weighing of the pros and
cons to decide. The biggest pro in this scenario is that the patient could be completely
rid of Alzheimer’s disease and would thankfully not have to endure the slow and
emotionally painful decline presented by the disease. Worst-case scenario the
treatment goes horribly wrong and the patient tragically passes away. This controversy
deserves serious thought by a group of diverse doctors, researchers, and scientists
because until it is deemed ethical to proceed with this treatment option, clinical trials
cannot be conducted, and the advancement of this method of treatment will halt.
Alzheimer’s also presents another ethical controversy that has been debated for
some time now. That is whether or not it is ethical to assist a patient with suicide by
drug overdose. Most argue it is unethical and should be outlawed but some argue the
opposite that it is unethical to force a patient to go on living as their life slowly fades
away. Is it better to let the patient go while they still understand what is going on in the
world around them, so that their loved ones remember how they were at their best? Or
is it better to prolong the life of the patient, so they may have more time to spend with
their families? After all, different patients react differently to each treatment option. It is
entirely possible for a patient to respond miraculously well to a particular treatment
option and prolong their life several years, even though it is impossible to repair the
damage already done by the disease. The most commonly prescribed medicine to
patients with Alzheimer’s disease is a type of cholinesterase inhibitor, a medication that
prevents the breakdown of acetylcholine, which is an important neurotransmitter in the
brain. The problem with this kind of medication is that as mentioned before,
unfortunately it does not reverse or repair the damages that have already been done. It
is important to realize the presence of the disease in its early stages so that the
medicine can be effective in prolonging the functionality of the brain.
This fact begs the question; is it better for someone to learn they have
Alzheimer’s in their early life so as to be better prepared? Or is it better to live life worry
free until one day the disease starts to show its symptoms? There are pros and cons to
both of these options. If someone knows they are going to develop Alzheimer’s
disease, they unfortunately have to live in fear that the symptoms could begin at any
time but they have a strong advantage in the fact that they can do everything in their
power to prevent those symptoms. The pro of not knowing is that one can live
ignorantly and blissfully but the downside is that unfortunately for those who are
unaware of the disease’s presence, no preventative measures will have been taken
when the symptoms of the disease begin.
In a perfect world the discovery of a cure for Alzheimer’s disease and all other
diseases related to mitochondrial dysfunction is in the near future. The understanding
of the relationship between mitochondrial dysfunction and Alzheimer’s disease is
growing exponentially as technological innovations are rapidly surfacing. It is probable
that in the next decade or so scientists and researchers will be close to arriving at a
sure fire method of curing Alzheimer’s disease. As of right now, not enough is known
about the genetics of the disease to effectively cure it through the use of gene therapy
although this method shows promise. If in the future further research of viral vectors is
conducted, not only will Alzheimer’s have a cure but several other genetic diseases and
diseases related to mitochondrial dysfunction will as well. The ethical issues
surrounding this disease will disappear once a cure is discovered that is consistently
successful from patient to patient. Only research in the years to come will support or
reject the hypothesis that mitochondrial dysfunction and Alzheimer’s disease are
associated with one another.
Cited References
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