BY: MARIE DOWD

CREUTZFELDT-JAKOB DISEASE

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

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

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

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

THE BRAIN • Cerebral Cortex- Outer covering of gray matter over the

hemispheres• Function: Interprets input and maintains cognitive function• Contains areas directly related to:VisionHearingSomatic SensationProduction of limb & eye movements• Neocortex- Most of the brain, contains 10-14 billion

neurons• Covers outer part of cerebrum and cerebellum

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

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]

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

POLYMORPHISM M129V

• Polymorphism that appears to influence the risk of developing a prion disease

EARLY SIGNS OF CJD Rapidly progressive

dementiaDepressionAgitationAnxiety DisorientationPersonality changesImpaired judgment &

thinkingDecline in intellectual

function

EARLY SYMPTOMS OF CJD

•Difficulty coordinating movements•No fever or flu-like symptoms •Difficulty walking•Unsteadiness•Muscle stiffness•Vision problems•Twitching

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

FOUR FORMS OF CJD

Sporadic CJDSuggested that a normal

brain protein undergoes an abnormal change and turns into a prion

Inherited CJDGene inherited from parent

carries mutation that causes formation of prions

Iatrogenic CJDInfection is accidently spread

by someone with CJD through medical or surgical treatment

Variant CJDCaused by consuming meat

from a cow that has been infected with BSE (“Mad Cow Disease”)

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

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

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

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.)

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

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

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

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

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”

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”

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