Download PRION DISEASE 101 Prions are infectious proteins that cause prion

PRION DISEASE 101
Prions are infectious proteins that cause prion diseases. We all have normal prion
proteins (PrPc, c=cellular) that can change shape and result in abnormal prion
proteins that cause disease (PrPSc, Sc=scrapie). These abnormal proteins can change
normal prion proteins into more abnormal prion proteins (Fig 1).
Figure 1
In animals, prion diseases
include scrapie (sheep and
goat), bovine spongiform
encephalopathy (cattle), and
chronic wasting disease
(deer, elk, moose). PrPSc
makes holes in the brain
tissue, making it have a
“spongy” appearance (Fig 2).
Human Prion Disease Types
Figure 2
In humans, there are three types of prion disease. The
most common cause of human prion disease is sporadic
(sporadic Creutzfeldt-Jakob disease or sCJD), which
makes up 85% of all cases and is thought to be due to a
spontaneous misfolding of PrPc into PrPSc. 10-15% of
cases are due to a genetic mutation of the prion protein
gene (PRNP). There are over 30 different types of
mutations and sometimes the disease is named
differently due to the way it appears clinically and
underneath the microscope. Genetic prion diseases
include genetic CJD (gCJD), Gerstmann-SträusslerScheinker disease (GSS), and fatal familial insomnia
(FFI). In genetic prion disease, every direct blood
relative has a 50% change of carrying the mutation.
In very specific circumstances, prion disease may be transmitted to another
individual leading to a third type of disease (acquired prion disease). The
transmissible nature of the illness was first discovered with the disease kuru, in
which disease was transmitted between members of the Fore tribe in Papua New
Guinea by ritualistic cannibalism. Iatrogenic CJD (iCJD) is due to transmission of
prion disease through specific medical procedures like human growth hormone and
corneal and dura mater transplants obtained from cadavers affected by prion
disease. Variant CJD (vCJD) is a very rare form of prion disease caused by the
ingestion of food contaminated with bovine spongiform encephalopathy (BSE). The
vast majority of these cases have occurred in European countries, where the BSE
epidemic occurred.
Frequency of Occurrence
Human prion diseases differ from other progressive brain diseases such as
Alzheimer's disease and Parkinson's disease in many ways, including their rarity.
There are approximately 1-2 new cases of prion disease per year per 1 million
individuals. Stated a different way, about 1 in 10,000 deaths in the U.S. are due to
prion disease. Most cases occur in mid to late life and the majority of individuals
affected by prion disease pass within one year of symptom onset.
Symptoms and Disease Progression
Patients affected by prion disease can have many different symptoms including
dementia (problems thinking), problems with their walking and/or coordination
(“drunken” gait), problems with their vision such as their depth perceptions or
double vision, weakness, tremors, and twitches (i.e., myoclonus). Most patients do
not pass from the disease itself, but from complications of the disease such as
pneumonia and other infections.
Diagnostic Tests
Although the only way to definitely diagnose prion disease is to examine the brain
tissue at autopsy, several diagnostic tests are used to help make a diagnosis during
life. The EEG (electroencephalogram) is used to look at brain waves and sometimes
can demonstrate a very specific pattern that is highly suggestive of prion disease
(i.e., periodic sharp wave complexes). The brain MRI is a type of brain scan that can
also show findings that are highly suggestive of prion disease. Areas on the outside
(cortex) and middle (basal ganglia) parts of the brain light up brightly on certain
brain MRI sequences. Finally, a lumbar puncture (spinal tap) can examine various
proteins in an individual’s spinal fluid. Two commonly examined proteins, 14-3-3
and tau, are often elevated in patients with prion disease, but can also be elevated in
other conditions. A newer test, RT-QuIC (real time quaking induced conversion),
can detect the actual abnormal prion protein and is 98.5% diagnostic of prion
disease should it be detected in the spinal fluid.
An autopsy is often recommended once a patient passes of suspected prion disease.
There are multiple reasons for this, including helping with the country’s surveillance
of prion disease to make sure that we do not have vCJD or other acquired prion
diseases occurring in our country. Autopsies also help detect new forms of prion
disease that may occur and this was how vCJD was first discovered. Autopsy also
provides a definite diagnosis for family members and genetic testing can also be
done should the family desire it.
Transmissible, not Infectious
Finally, we often hear about family members’ fears of possibly catching prion
disease from their loved one. Prion disease requires very specific scenarios for it to
be transmitted to another individual. None of these scenarios would occur with
routine care and contact of a loved one.
Source:
Brian Appleby, MD
Co-Director, National Prion Disease Pathology Surveillance Center
Associate Professor, Departments of Neurology, Psychiatry, & Pathology
Case Western Reserve University School of Medicine
Co-Medical Director, CJD Foundation Board of Directors; Cleveland, Ohio