1. Creutzfeldt-Jakob’s Disease
(CJD)
Brady Douglas

2. Neurodegenerative disorder that
leads to complete loss of brain
function and ultimately death

3. - Caused by infectious agents called prions.
- A prion is an abnormally folded protein
that promotes the misfolding of it’s
native counterparts
- Prions are resistant to proteases

4. CJD is just one of many different types of Transmissible Spongiform
Encephalopathies caused by prion proteins
*Transmissible
Spongiform
Encephalopathy
Affects Animals
Bovine Spongiform
Encephalopathy
Endemic Sheep Scrapie
“Mad-Cow Disease”
Chronic Wasting
Disease
Affects Humans
Gerstmann-Sträussler-
Scheinke
Encephalopathy
Kuru
Fatal familial
Insomnia
Creutzfeldt-Jakob’s
Disease
Classic CJD
Sporadic/Spontaneous
Familial/Hereditary
Variant CJD
iatrogenic

5. History of CJD
• 1920s: CJD condition first described by German
neurologists Hans Gerhard Creutzfeldt and Alfons
Maria Jakob
– It became infamously known as a rare form of dementia
that was incurable and universally fatal
• 1980s: BSE epidemic in the UK (> 1 million cows)
http://news.discovery.com/animals/mad-cow-disease-causes-cattle-eyes-to-glow.html

6. History of CJD
• 1983: Famous Choreographer George
Blanchine dies of CJD
• 1994: first case of BSE in humans (link was first
established)
• 1996: New disease related to BSE was first
reported, defined as a “new variant” of CJD
(vCJD)
• Today: Since the first case of vCJD, the
following cases have been reported: 163 cases
in the United Kingdom, 23 in France, 4 in
Ireland, 3 in the United States, 3 in Spain, 2 in
the Netherlands, 2 in Portugal, 1 in Italy, 1 in
Canada, 1 in Saudi Arabia and 1 in Japan.

7. Genetic Component
• Familial forms of CJD can be acquired by
inherited mutations to the PRNP gene.
• 10-15% of CJD cases are inherited
• Mode of inheritance: Autosomal Dominant
(one mutated copy of the gene is sufficient to
acquire this disease, can be inherited from a
single parent)
• Infected individual has a family history of CJD
and/or tests positive for the mutated gene.

8. Other Forms of CJD
• Sporadic/Idiopathic (85% of cases)
– Disease arises spontaneously, unsure of it’s origin
– Usually appears later in life (between 50 to 75)
and kills 90% of patients within a year
– Patients had no known risk factors
– 1/1,000,000 people affected annually worldwide
– Approximately 200 are at risk every year in the
USA
– Possible cause: random mutation of the PRNP
gene

9. Other Forms of CJD
• Iatrogenic (vCJD)
– Rarest form, affecting less than 1% of patients
– Common in younger patients ( > 40 years old)
– Can be acquired through various routes
 Ingestion of meat products contaminated with BSE
 Blood transmission from an affected individual
 Use of plasma derived medications from an affected
individual
• Exposure to infected brain tissue or spinal cord fluid through
medical procedures, i.e., dura mater grafts, corneal
transplants, skin transplants, or the implantation of tainted
stereotactic electrodes or surgical instruments.

10. Genetic Location of the Prion Protein
• Cytogenetic location: 20p13
• Genomic coordinates
(GRCh37): 20:4,666,796 -
4,682,233
• From NCBI
(http://omim.org/entry/17664
0)
(http://fr.wikipedia.org/wiki/Chromosome_20_humain)

11. Phenotypic Manifestation
• 4 basic physiological characteristics (shared by all TSEs)
– Spongiform appearance of brain tissue; many tiny holes`
visible by the naked eye.
– Neuronal Loss.
– Astrocytosis- unusually large amount of astrocytes in the
brain tissue due to the destruction of nearby neurons.
– Amyloid plaques formed by aggregates of the prion
protein.
http://www.humenhealth.com/creutzfeldt-jakob-disease-cjd

12. • The normal prion protein is water soluble and is dominated by
alpha helices. It resides in the plasma membranes of lymphocytes
(transmissible by blood)
• The diseased prion is water insoluble and is dominated by beta
sheets. This conformation favors the formation of the detrimental
protein aggregates that lead to chronic dementia and death
• http://www.riversideonline.com/health_reference/Infectious-
Disease/DS00531.cfm
• http://www.cdc.gov/ncidod/dvrd/cjd/classic_cjd_tissue_slide_large
_view.htm

13. Symptoms
– Headaches
– Anxiety
– Insomnia
– Depression
– Behavioral changes
– Agitation
– Confusion
– Memory loss
– Impaired Judgment
– Lack of Muscle
Coordination
– Speech and visual
problems
The disease process can be broken down into 3 clinical
phases:
First stage: Subtle symptoms, often overlooked as other
problems

14. Symptoms
– Spasticity
– Rigidity
– Myoclonic jerks
– Limb weakness
The disease process can be broken down into 3 clinical
phases:
Second stage: Rapid mental deterioration, severe
dementia state within 6 months

15. Symptoms
– Completely bedridden
– Blind
– Mute
– Glazed, vacant stares
– Myoclonic seizures
– Increased susceptibility
to heart/respiratory
failure, pneumonia and
other infections
– Most lapse into a coma
before death
The disease process can be broken down into 3 clinical
phases:
Third stage: Terminal stage

16. How to detect/cure this disease?
• CJD is still an incurable disease as of today
• No single confirmatory test as of today, can
only rule out other forms of dementia and
curable encephalopathies.
• Only true way to confirm CJD pre-mortem is a
biopsy of the brain tissue, but by this time,
dementia has already progressed well into the
second stage.

17. Approaches to Treatment
• Find and isolate agents that reduce PRPN
expression, or that destabilize the mature form
– Congo red
• Gene Therapy
– In most species, genes encoding protease resistant
products are considered to be errors and are inhibited
by the natural machinery
– Could it be possible to incorporate these genes into
our genome?
– Must continue to increase our knowledge

18. Current Research Shows Infectious Prions Can Arise
Spontaneously in Normal Brain Tissue
• Recent new study (2010) shows that spontaneous
appearances of prions in healthy brain tissue can
be promoted by contact with steel surfaces.
• Participants: Scripps Research Institute in Florida
and the University College London (UCL) Institute
of Neurology in England

19. Citations
Cyngiser, Tracy A. "Creutzfeldt-Jakob Disease: A Disease Overview." American
Journal of Electroneruodiagnostic Technology 48 (2008): 199-208.
Heath, C. A., Cooper, S.A., Murray, K., Lowman, A., Henry, C., MacLeod, M.A.,
...Will, R.G. (2010). Validation of diagnostic criteria for variant Creutzfeldt-
Jakob disease. Annals of Neurology, 67(6), 761-770.
Kelechi, Robert, and Ferdinand C. Nwanebu. "Prion and Prion Diseases."
African Journal of Clinical and Experimental Microbiology 8.2 (2007): 38-
52.
Liras, Antonio. "The Variant Creutzfeldt-Jakob Disease: Risk, Uncertainty or
Safety in the Use of Blood and Blood Derivatives?" (2008). International
Archives of Medicine. Web.
<http://www.intarchmed.com/content/1/1/9>.
Manuelidis, Laura, Ying Liu, and Brian Mullins. "Strain-specific Viral Properties
of Variant Creutzfeldt-Jakob Disease (vCJD) Are Encoded by the Agent and
Not by Host Prion Protein." J Cell Biochem. 106.2 (2009): 220-31. NIH
Public Access. Web.
"News Release." The Scripps Research Institute. UK Medical Research Council,
26 July 2010. Web. 26 Sept. 2011.
<http://www.scripps.edu/news/press/20100726.html>.