2. WHAT IS CREUTZFELDT-JAKOB DISEASE (CJD)?
• Form of Transmissible
Spongiform
Encephalopathy (TSE)
• Invariably fatal
• Brain disorder
• Caused by prion
proteins in brain tissue
• Rapidly progressive
dementia
3. WHAT IS A PRION?
• Abnormal, pathogenic
agents
• Transmissible
• Induce abnormal folding
of normal cellular proteins
• Affects prion proteins—
found most abundantly in
the brain
• Abnormal folding leads
to brain damage
(destruction of neurons)
• Occur in two forms
4. WHAT IS A PRION? (CONT.)
• Appear to remain
infectious after being
exposed to treatments
that destroy nucleic acids
• Transmitted by eating &
inoculation directly into
brain or into skin/muscle
tissue
• Cannot be destroyed by
boiling, alcohol, acid, or
radiation
Widely accepted prion
theory…
The cellular protein PrP is
the sole causative agent
of prion diseases—no
nucleic acid involved
Prion theory not proven to be
correct, but supported by
evidence
5. PRION DISEASES
• Family of rare progressive
neurodegenerative
disorders
• Cause changes in memory,
personality and behavior
• Impair brain function
• Cause difficulty with
coordination of movements
• Domino effect
6. THE BRAIN
• Cerebral Cortex- Outer covering of gray matter over the
hemispheres
• Function: Interprets input and maintains cognitive
function
• Contains areas directly related to:
Vision
Hearing
Somatic Sensation
Production of limb & eye movements
• Neocortex- Most of the brain, contains 10-14 billion
neurons
• Covers outer part of cerebrum and cerebellum
7. THE BRAIN (CONT.)
• Folds in the brain
add to surface area
• Increase amount of
gray matter &
quantity of info that
can be processed
• Some areas critical
for thinking &
reasoning
8. NORMAL FUNCTION OF PRNP GENE
• Belongs to a family of genes called
antigens
• Provides instructions for making prion
proteins
• Active in the brain and several other
tissues
• Researchers believe function is to
transport copper into cells & protect
brain cells
• A role suggested in the formation of
synapses [neurons]
9. PRNP GENE MUTATION
• Normally in a stable shape
that does NOT cause
disease, but can be flipped
into an abnormal shape
• Determined by magnetic
resonance image analysis
• Mutations clustered within
or adjacent to key structural
elements in protein
• Some change single AA
others insert additional AA
into protein
11. EARLY SIGNS OF CJD
Rapidly progressive
dementia
Depression
Agitation
Anxiety
Disorientation
Personality changes
Impaired judgment &
thinking
Decline in intellectual
function
12. EARLY SYMPTOMS OF CJD
•Difficulty coordinating
movements
•No fever or flu-like
symptoms
•Difficulty walking
•Unsteadiness
•Muscle stiffness
•Vision problems
•Twitching
13. LATER SIGNS AND SYMPTOMS OF CJD
• Mental impairment more severe as illness progresses
• Often develop involuntary muscle jerks
• Ability to speak & move are lost
• Individual may enter a coma
• Causes more rapid deterioration of an individual’s
abilities than Alzheimer's or Dementia
• Often leads to…
Heart failure
Respiratory failure
Pneumonia
Infection
14. FOUR FORMS OF CJD
Sporadic CJD
Suggested that a normal
brain protein undergoes an
abnormal change and turns
into a prion
Inherited CJD
Gene inherited from parent
carries mutation that causes
formation of prions
Iatrogenic CJD
Infection is accidently spread
by someone with CJD
through medical or surgical
treatment
Variant CJD
Caused by consuming meat
from a cow that has been
infected with BSE (“Mad
Cow Disease”)
15. INHERITED CJD
• Genetic mutation of the
prion protein
• Mutation causes the
formation of prions in their
brain during adulthood
• Less than 15% of cases
• Age of onset younger
• Duration of illness longer
• Affect people in their 50s
• 10 deaths in the UK in
2012
16. IATROGENIC CJD
• Infection is accidently
spread from someone
with CJD through
medical or surgical
treatment
• Common cause—growth
hormone treatment using
human pituitary growth
hormones
17. VARIANT CJD
• Caused by consuming
meat from an infected
cow with BSE
• Link between CJD and
BSE made in 1996
• Begins with psychiatric
symptoms
• Signs include muscle
paralysis & tremors
• Sensations of cold or pain
• Age of onset typically
younger
• Incubation period can
last up to 10 years
• Duration of illness 13-14
months
18. SPORADIC CJD
• 80-85% of cases
• Strikes people age 45-75,
symptoms develop in 60s
• No known family history of
the disease
• Duration of illness shorter
than other forms
• Change occurs
spontaneously
• No firm link between CJD
and risk factors (age,
occupation, diet, etc.)
19. CJD DIAGNOSTIC TESTS
• MRI brain scans can reveal
patterns of brain
degeneration, signifying a
prion disease
• Spinal tap performed to rule
out other diseases but
CANNOT be used alone to
diagnose CJD
• Tonsillar biopsy is a useful
test
• Brainwave pattern shown
during an EEG is abnormal
in vCJD patients
20. WHAT ARE THEY RESEARCHING?
• Unique nature of proteins
• Factors that influence
susceptibility to the disease
• New diagnostic tests that
will be able to detect CJD
before symptoms appear
• The use of antibodies for the
prevention & treatment of
prion diseases
• Development of a CJD
vaccine
21. CURRENT RESEARCH
• Researchers created 3-D
brain-like tissue to study
brain injuries & diseases
• First used to test reaction of
a brain on drugs
• Developed at Taft
University’s Tissue
Engineering Resource
Center
• Can be maintained for 2
months in labs—helpful for
studying long-lasting
neurological diseases
22. CURRENT RESEARCH (CONT.)
• Using rodent models of
the disease and brain
tissues from autopsies
• Part of mouse is fused
with the human gene
to infect mice with CJD
• Looking for factors that
influence susceptibility
to the disease
• Hoping to develop
effective treatments for
patients with CJD
23. VIEW FROM MEDICAL PROFESSIONALS
• Laura Maneulids—section
chief of surgery in the
neuropathology
department at Yale
University
• Conducted a 1989 study
that found 13% of
Alzheimer's patients actually
died from CJD
• Suggests that more CJD
victims are going
undetected due to
misdiagnosing patients
“What people call Alzheimer's now is
more broad than what people used
to call it…that has the possibility of
encompassing more diseases”
24. VIEW FROM MEDICAL PROFESSIONALS
• Andrew Monjan—chief
of neuropsychology of
aging program
• Acknowledged the
increase in Alzheimer's
cases but suggested it
was “due to the aging
of the population”
25. FUN FACTS ABOUT CJD
• CJD has been recognized
since the early 1920s
• Average annual rate 4.6
cases per million
• Infected brains that have
been sitting in
formaldehyde for decades
can still transmit CJD
• 33% of patients with
sporadic CJD, prion proteins
found in skeletal muscle
and/or spleen
