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Sosie Yorki
Mrs. Greene
Capstone
21 September 2016
CMT and Alzheimers: Causes and Symptoms
Neurodegenerative diseases occur when neurons, or nerve cells, die and can no longer
instruct the muscle to perform commands by the brain, so patients end up struggling with daily
tasks. Charcot-Marie-Tooth disease, or CMT, is the most common hereditary neurodegenerative
disease that causes deformities in the feet, hands, and shins. Alzheimers disease, or AD, is wellknown to the general public for impacting cognitive ability in senior citizens. While
neurodegenerative diseases vary in symptoms, progression, and onset, CMT and AD are two
opposites, because CMT has entirely physical symptoms and Alzheimers has entirely mental
symptoms.
In CMT, a cause of neurodegeneration is mitochondrial dysfunction, while in
Alzheimers, a cause is deformation in the tau protein. Mitochondria are either constantly
dividing in a process called fission or coalescing in a process called fusion. The balance between
the rate of fusion and fission must be preserved in order to have a healthy mitochondrion. If
genetic mutations alter the balance, a mitochondrions ability to function and support its neuron
will decrease. For example, mutations in the Mfn2 gene cause mitochondria to undergo less
fusion than usual and perform less aerobic respiration, which can deprive neurons of energy and
force them to degenerate1. In patients with Alzheimers disease, nerve cells die due to amyloid
plaques and tangles of neurofibrils1. Amyloid plaques are abnormal clusters of membrane

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proteins that block molecular signals from passing through the synapse, or space between
neurons1. Neurofibrils are the railroad tracks for nerve impulses to travel on, and a protein called
tau keeps the neurofibrils in orderly, parallel rows. In AD, the tau protein is deformed and takes
on a double helix shape that forms tangles with the neurofibrils1. The deposition of amyloid
plaques and cluttering of neurofibrillary tangles blocks synapses and can destroy neurons.
Neuronal loss in CMT results in the physical and mental characteristics of the disease.
Concerning physical symptoms, there is much uncertainty about how they happen and what
exactly happens. A group of scientists aimed to clear the ambiguity and conducted clinical
examinations of patients with a type of CMT called CMT1A. In the patients, muscle weakness
was almost exclusively in distal muscles [or muscles in the legs near the feet] and [weakness]
appeared to progress from distal extensor [muscles that straighten limbs] to distal flexor muscles
[that bend at joints] rather than progressing [to proximal muscles] up the leg or arm. 2 Since the
neurons in distal muscles are longer than those in proximal muscles, this data suggests that
CMT1A degenerates in a length-dependent pattern and attacks muscles in the feet and legs2. This
same group also claims that loss of sensitivity, another symptom of CMT, could be explained by
the degeneration of sensory axons, or special extensions of neurons that make organisms feel
pain2. While it is confirmed that degeneration causes weakness and numbness, it is still
unconfirmed if it causes sleep apnea, a condition where ones breathing is interrupted while
asleep, and depression. Scientists know CMT patients are at an increased risk for these two
conditions but they dont know why or how3. Sleep apnea and depression could result from the
drastic change in lifestyle one experiences when he develops CMT or from neurological
impairment, but less data supports the latter. CMT is a distinctive neurodegenerative disease in
the way it deforms muscles in the feet and legs and makes them weak and numb.

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Mental symptoms characterize Alzheimers more than its physical ones. AD patients can
experience psychosis, or a mental disorder that can result from delusion and hallucination,
accompany agitation and anxiety, and accelerate memory loss5. The networks in the frontal
cortical brain lobe and the circuit of neurons in the anterior cingulate cortex of the brain support
the emotional capabilities that degenerate in the progression of psychosis, so neuron dysfunction
in those regions could cause it5. Neurodegeneration in certain brain regions cause physical side
effects such as difficulty in talking, abnormal posture and gait, and muscle rigidity but the mental
symptoms are more of what characterizes the disease4. The symptoms for AD are less defined
than those of CMT because CMT was discovered sooner, but research for all neurodegenerative
diseases can still catch up with modern demand by employing advanced technology and
producing more reliable data.
Future scientific research for CMT and Alzheimers could confirm the symptoms and
cause of each one by looking at a wide variety of test subjects, as opposed to weak, current
research that lacks diversity in age, sex and severity of disease in test subjects. Once symptoms
and causes are confirmed, new treatments could be developed to target specific symptoms.
Responsibility for future research must be held on the public as well. With increased awareness,
more patients will be concerned about CMT, and doctors will be coerced to learn about and
specialize in the disease. More pressure will be placed on scientists to find a cure and more
donations to charities such as the CMT Association and Alzheimers Association will help
properly fund scientific research.

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References
1. Itoh K, Nakamura K, Iijima M, Sesaki H. Mitochondrial Dynamics in
Neurodegeneration. Trends in Cell Biology. 2013; 23(2): 64-71. doi:
10.1016/j.tcb.2012.10.006.
2. Krajewski, KM, Lewis, RA, Fuerst, Dr, et al. Neurological Dysfunction and Axonal
Degeneration in CharcotMarieTooth Disease Type 1A. Brain. 2000; 123 (7): 15161527. doi: http://dx.doi.org/10.1093/brain/123.7.1516.
3. Cordeiro J, Marques W, Hallack JEC, Osrio FL. Charcot-Marie-Tooth Disease,
Psychiatric Indicators and Quality of Life: A Systematic Review. ASN Neuro. 2014;
6(3): e00145. doi: 10.1042/AN20130048.
4. Tsolaki M, Kokarida K, Iakovidou V, Stilopoulos E, Meimaris J, Kazis A.
Extrapyramidal Signs and Symptoms in Alzheimers Disease: Prevalence and
Correlation with The First Symptom. American Journal of Alzheimers Disease and
Other Dementias. 2001; 16(5): 268-278. doi: 10.1177/153331750101600512.
5. Mega M, Lee L, Dinov I, Mishkin F, Toga A, Cummings J. Cerebral Correlates of
Psychotic Symptoms in Alzheimers Disease. Journal of Neurology, Neurosurgery &
Psychiatry. 2000; 69(2): 167-171. doi: 10.1136/jnnp.69.2.167.