Running head: CREUTZFELDT-JAKOB DISEASE

Creutzfeldt-Jakob Disease

Alexis Ray

Honors Biochemistry

Mr. Keith

DuBois Area High School

Author Note

Alexis Ray, the author of this research paper, is currently a student enrolled in Honors

Biochemistry.

Abstract

Creutzfeldt-Jakob Disease is a rare brain disorder, but it is the most common type of prion

disease. According to the National Institute of Health, Creutzfeldt-Jakob Disease, or CJD, only

affects “one person in every one million people per year worldwide; in the United States there are

about 300 cases per year”. CJD affects older individuals between the ages of 55 to 80 years old.

The symptoms are similar to those of other progressive dementias such as Alzheimer’s Disease.

There are three known types of CJD, sporadic, hereditary, and acquired. It is a degenerative

disease that affects the cerebral cortex of the brain (nobelprize.org). Sponge-like tissues will result

when brain tissue is affected by prion diseases.

Keywords: Creutzfeldt-Jakob Disease, Prion Diseases, Progressive Brain Disease,

Degenerative Disease

Creutzfeldt-Jakob Disease
CREUTZFELDT-JAKOB DISEASE 1

Introduction

Named for the neurologists who first described it in 1920, Creutzfeldt-Jakob Disease, or

classic CJD, is a chronic brain degenerative disorder. Classic CJD belongs to a group of animal

and human diseases known as Transmissible Spongiform Encephalopathies (TSEs). TSEs, also

known as prion diseases, affect the brain and the nervous system. The term spongiform comes

from the characteristic appearance of infected brains, filled with holes until they resemble sponges

under a microscope (see Appendix A). There are many different variants of CJD, one being

Bovine Spongiform Encephalopathy (BSE) also known as “Mad Cow” disease which is a form of

variant CJD (vCJD), distinct from classic CJD. This disease is rapidly progressive and leads to

death within the first year of initial illness(National Institute of Health, 2017). There are three

known types of classic CJD. Sporadic CJD occurs with no recognizable pattern of transmission,

the patient might not show any known risk factors of the disease. This is the most common type

of classic CJD affecting 85% of those infected. Hereditary CJD is the second most common type,

effecting 5-10% of those infected. Hereditary CJD includes people with a family history of mental

illness and/or test positive for a genetic mutation also diagnosed with classic CDJ. The third and

least common type of classic CJD is acquired. In order to acquire classic CJD a person must be

exposed to brain or nervous system tissue that is infected with the disease. Surgeons, medical

practitioners, and morticians are at risk for this type of CJD (U.S. Department of Health and

Human Resources, 2017). There is not any evidence that classic CJD is contagious through casual

contact. Different hypotheses are being investigated however, there is still more research to be

done concerning this fast-paced brain disease, therefore there are many unknowns that remain.

History
CREUTZFELDT-JAKOB DISEASE 2

Classic CJD was first described in the early 1920s by German neurologist Hans Gerhard

Creutzfeldt and then shortly after that by another neurologist, Alfons Maria Jakob. Their studies

and reports document clinical discoveries that do not agree with some of the current symptoms

and criteria for classic CJD. They were however, the first to report several other instances in

which the patients consistently suffered from the same types of neurological and physiological

symptoms associated with classical CJD as it is defined today. Later in the 1930s, another

German scientist, Friedrich Meggendorfer, described a case of hereditary CJD in northern

Germany. From then on, cases of CJD and variations of the disease have been reported all over

the world. In Australia, following a blood transfusion, a case of CJD was reported. This brought

about fear and confusion as to what this mysterious CJD disease was and how to avoid it. The

first documented case in the United States was in 1988, in Manchester, New Hampshire. Just

recently, in 2013, another case of CJD was confirmed in New Hampshire(Centers for Disease

Control, 2013). Overtime, knowledge of classic CJD and other TSEs grew and cases were

reported and recorded. Cases were reported in Texas however, there was not a common pattern

between the people affected, and when they were diagnosed (See Appendix C).

Diagnosis, Symptoms, and Care

Some of the signs and symptoms of onset classic CJD are characterized by muscular

discoordination, personality changes, and impaired memory along with depression, insomnia, and

impaired vision. Onset symptoms usually occur in patients As time progresses and the patient’s

condition worsens, the symptoms rapidly decline. Mental impairment will become severe and the

individual will eventually lose the ability to move and speak, then entering a coma. Individuals

may also contract other illnesses such as pneumonia, that could lead to death(Editors of

Encyclopaedia Britannica, 2018). The problem medical professionals are experiencing when it
CREUTZFELDT-JAKOB DISEASE 3

comes to diagnosing a patient with this disease is that many of the symptoms of CJD are those of

many other, more common progressive neurological disorders such as Alzheimer’s Disease and

other types of dementia as well (National Institute of Health, 2017). As of today, the only way to

confirm a case of CJD, is to perform a brain autopsy or biopsy.

In order to diagnosis CJD, a medical professional will have to perform multiple tests. This

is done to rule out any other treatable type of dementia, because many of them have the same

symptoms. In the first round of testing, a physician will perform a neurological exam. They will

then consult with other physicians. A diagnostic test will include a spinal tap. The spinal tap will

be used to test for other types of dementia. After those two test and the results have come back, an

electroencephalogram (EEG) will be taken to measure and record the brain’s electrical pattern.

The EEG test is particularly valuable because it is able to show the specific type of abnormality a

patient is experiencing if they have classic CJD. Another strategy the doctors and physicians may

use is computerized tomography. Computerized tomography of the brain would be able to rule out

the possibility that the symptoms might be related to a stroke, brain tumor, or some other type of

previous brain injury. Magnetic Resonance Imaging (MRI) brain scans are also a valuable tool

when it comes to diagnosis of brain disorders because they are able to reveal patterns of brain

degeneration that could help rule out further diseases and disorders (National Institute of Health,

2017). The last resort in diagnosis of classic CJD and other variations of the disorder is a brain

biopsy or autopsy. Both of these procedures put the doctors and surgeons performing the

examination at high risk to contract the disease themselves.

Classic CJD and other diseases like it are not curable. Medical researchers have tested

various types of drugs but none of them have shown any human benefit or improvement

consistently. The only way to treat this disease is to try to alleviate as much pain and suffering as
CREUTZFELDT-JAKOB DISEASE 4

possible. Medical professionals may prescribe opiate drugs or Clonazepam to relieve involuntary

muscle twitching in the early stages of the disease (The Health Information Network, n.d.). Other

activities that could alleviate some pain and suffering include remaining active for as long as the

patient can then once the patient becomes bedridden, catheters and feeding tubes could be used to

reduce some of the pain.

Types and Variations

Classical CJD is one type of Creutzfeldt-Jakob Disease. There are other forms and

variations that are related to classical CJD, but are distinctly different. Variations of classical CJD

include illness in both animals and humans. These variations of CJD are also known as

prion diseases. Prion diseases as a group are a family of rare progressive neurodegenerative

disorders(US Department of Health and Human Resources, 2017). An example of this is Bovine

Spongiform Encephalopathy (BSE) or more commonly known as “mad cow” disease. BSE is

frequently confused with classical CJD because of their similar symptoms. However, BSE only

affects cattle, humans contracted variant CJD by consuming infected tissues from the cattle

(Stoppler, M.C.). There have only been around 200 cases of variant Creutzfeldt-Jakob Disease

(vCJD) reported, but because of the unknowns associated with the disease, it struck fear into the

hearts of millions of people all around the world. Other variations within the family classified as

Prion diseases include, Kuru and Gerstmann-Straussler-Scheinker Syndrome. Both of these

diseases are brain degenerative diseases that affect humans, while other disorders such as chronic

wasting disease (CWD) and scrapie affect animals. The diseases listed are very different in the

ways they are contracted and how the subject is affected physiologically however, they are very

similar in the ways in which they affect the brain and their mental ability.

Prions and Research

CREUTZFELDT-JAKOB DISEASE 5

Prions are small proteins that when in an incorrect formation, become infectious disease-

causing agents. A prion is not bacterial, fungal, or viral, and does not contain any genetic

material. A neurologist, Stanley Prusiner, coined the term proteinaceous infectious particle in

1982 as part of a hypothesis regarding minor infections similar to other degenerative disease, such

as kuru. Prusiner was also responsible for developing the modern model of the prion(Bruner,

2016). The model of the toxic protein is an altered form of the normal cellular protein. Prions are

believed to be one of the smallest infectious particles in the human body. Variations in the shape

in which a prion protein is folded determines what part of the brain it will affect. The variations in

shape are known as conformations(See Appendix B). Prions have been held responsible for

several brain degenerative diseases, including TSEs and classic CJD.

Prions and diseases associated with them are poorly understood due to the technology we

have today and fascinating to the medical community. They have been the subject of two nobel

prizes in physiology and medicine. These diseases are very rare and difficult to transmit. It has

been suggested that the prion is the misfolded protein that causes other cellular proteins to change

their conformation into misfolded forms as well. Prions have been called, “self-replicating

proteins”. They have been given this name because they possess the ability to induce abnormal

folding of normal molecules.

Manganese has been suggested as a possible cause of CJD and other variations of the

disease. Scientists have tried to link an excess of manganese in the human body to eventual CJD.

Research is still being done and the effects are still being studied however, scientists believe that

the excess of manganese causes a chain reaction in the body. Manganese can disrupt the structural

stabilization and activation of glutamine synthase. This could lead to the accumulation of

neurotoxic glutamate as opposed to glutamine. Another theory involves the binding of

CREUTZFELDT-JAKOB DISEASE 6

glycosaminoglycans to glycoproteins. Glycosaminoglycans bind to glycoproteins in order to

protect the glycoproteins from binding with any abnormal prions. Manganese can cause an excess

of lectins in the body. A specific type of lectin, concanavalin A, has been known to bind to

glycosaminoglycans, prohibiting them from protecting glycoproteins from abnormal prions.

These are medical hypotheses and evidence to support them is still being investigated(The Health

Information Network, n.d.).

There are foundations dedicated to the pursuit of knowledge regarding CJD and a cure for

the degenerative disease and others like it. The Creutzfeldt-Jakob Disease Foundation,

Incorporated is a notorious organization dedicated to furthering the research on CJD and other

TSEs by donating thousands of dollars in research grants to scientists all around the world.

Classic CDJ and other TSEs like it still have many unknowns. They are very rare and perplexing

disorders and more information and better technology is needed to fully understand classic CJD

and other degenerative brain diseases(The CJD Foundation Inc., n.d.).

Conclusion and Future Outlook

Classic CJD and other variants of the disease, including TSEs will continue to fascinate

the medical community. Prions, the infectious protein thought to be responsible for these

degenerative diseases, are still in the process of being completely understood in science and

medicine. As of today, the cause of sporadically acquire classic CJD is still unknown, but there

are many theories and hypotheses being investigated. Research on the topic will continue to be

done in order to one day hopefully find a cure. Foundations like the Creutzfeldt-Jakob Disease

Foundation are taking the necessary steps in order to find a cure for the disease and other prion

diseases like it. Classic CJD is a rare disease, but that doesn’t mean it should be ignored.
CREUTZFELDT-JAKOB DISEASE 7

Resources

Bruner, Robert (2 Jan. 2016). Prions. Retrieved from

https://bio.libretexts.org/Core/Molecular_Biology_(Core)/Prions

Centers for Disease Control (6 Sept. 2013). Frequently Asked Questions on Creutzfeldt-

Jakob Disease (CJD) and Catholic Medical Center (CMC). Retrieved from

https://www.catholicmedicalcenter.org/uploads/FAQs_CJD_DHHS_CMC.pdf

The CJD Foundation Inc. (n.d.). Creutzfeldt-Jakob Disease Foundation, Inc. Retrieved

from https://cjdfoundation.org/

Editors of Encyclopædia Britannica (19 Jan. 2018). Creutzfeldt-Jakob Disease. Retrieved

from https://www.britannica.com/science/Creutzfeldt-Jakob-disease

Greenlee, John E. (18 Jun. 2017). Creutzfeldt-Jakob disease. Retrieved from

http://www.medlink.com/article/creutzfeldt-jakob_disease

The Health Information Network (n.d.). Creutzfeldt Jakob Disease. Retrieved from

http://www.nzhealth.net.nz/dis_ease/cjd.shtml

National Institute of Health (10 May 2017). Creutzfeldt-Jakob Disease Fact Sheet. Retrieved

from https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-

Sheets/Creutzfeldt-Jakob-Disease-Fact-Sheet

Nobelprize.org. Retrieved form

https://www.nobelprize.org/nobel_prizes/medicine/laureates/1997/illpres/brain.html

Safe and Healthy School Food Coalition/NYC (26 Apr. 2013). “What’s One More

Protein?”. Retrieved from http://schoolfood.info/?p=428

CREUTZFELDT-JAKOB DISEASE 8

Singeltary, Terry S. (19 Aug. 2011) Transmissible Spongiform Encephalopathy. Retrieved

from http://transmissiblespongiformencephalopathy.blogspot.com/2012/02/national-prion-

disease-pathology.html

U.S. Department of Health and Human Resources (17 Aug. 2017). Prion Diseases. Retrieved

from https://www.cdc.gov/prions/index.html

Appendix A:
CREUTZFELDT-JAKOB DISEASE 9

This is a tissue sample that exemplifies the sponge-like cavities in brain tissue of a CJD patient
(Editors of Encyclopaedia Britannica, 2018).

Appendix B:
CREUTZFELDT-JAKOB DISEASE 10

This image illustrates a normal prion protein, compared to an abnormal prion protein. The
abnormal prion protein is simply in a different conformation than the normal prion protein
however, the abnormal one is deadly and is likely to cause a brain degenerative disease depending
upon the specific abnormal conformation(Safe and Healthy School Food Coalition/NYC, 2013 ).

Appendix
C:
CREUTZFELDT-JAKOB DISEASE 11

This graph depicts the cases of classic CJD reported in Texas within the time span of 2000
to 2010(Singeltary, 2011).