Researchers find infectious prions in Creutzfeldt-Jakob disease patient skin

November 22, 2017, Case Western Reserve University
This micrograph of brain tissue reveals the cytoarchitectural histopathologic changes found in bovine spongiform encephalopathy. Image: Wikipedia

Creutzfeldt-Jakob disease (CJD)—the human equivalent of mad cow disease—is caused by rogue, misfolded protein aggregates termed prions, which are infectious and cause fatal damages in the patient's brain. CJD patients develop signature microscopic sponge-like holes in their brains. The initial signs of CJD include memory loss, behavior changes, movement disorder, and vision problems, which usually rapidly progress to death. According to the National Institutes of Health (NIH), 90 percent of CJD patients die within one year of onset, and hundreds of Americans are diagnosed annually. There is no available treatment or cure.

There are numerous types of prion diseases in humans, and CJD is the most common. About 90 percent of CJD cases have a sporadic origin. Prion infectivity is highly concentrated in CJD patient tissue. Inter-personal CJD transmission has occurred after patients were exposed to surgical tools previously contaminated by CJD brain tissues.

But in a Science Translational Medicine study published today, Case Western Reserve University School of Medicine researchers found that CJD patients also harbor infectious prions in their , albeit at lower levels. In the study, the researchers collected skin samples from 38 patients with assistance from the National Prion Disease Pathology Surveillance Center at Case Western Reserve School of Medicine and measured their prion levels. Using a highly sensitive in vitro assay developed and conducted by Byron Caughey's group at the NIH, they detected prion protein aggregates in the skin samples from all of CJD patients. Prion levels were 1,000-100,000 times lower in the skin than in the brain, and only detectable by this extremely sensitive assay. The researchers further demonstrated that such skin prions are infectious, since they are capable of causing disease in humanized mouse models.

Credit: Case Western Reserve University

This unexpected finding raises a host of issues. "It is well known that CJD is transmissible via surgical or medical procedures involving prion-infected brain tissue. Our finding of infectious prions in skin is important since it not only raises concerns about the potential for disease transmission via common surgeries not involving the brain, but also suggests that skin biopsies and autopsies may enhance pre-mortem and post-mortem CJD diagnosis," said Wenquan Zou, Associate Professor of Pathology and Neurology and Associate Director of the National Prion Disease Pathology Surveillance Center at Case Western Reserve School of Medicine. Zou led the study involving a consortium of research groups and researchers across Case Western Reserve School of Medicine, University Hospitals Cleveland Medical Center, the NIH, and the People's Republic of China.

"The level of prion infectivity detected in CJD skin was surprisingly significant, but still much lower than that in CJD brains," cautioned Qingzhong Kong, Associate Professor of Pathology and Neurology at Case Western Reserve School of Medicine. "Prion transmission risk from surgical instruments contaminated by skin prions should be much lower than that of instruments contaminated by brain tissue." In the study, the Kong group assisted by the Zou group demonstrated that CJD patient skin is infectious using humanized transgenic mouse models.

Current diagnostic tools for CJD rely on brain tissue samples collected at either biopsy or autopsy, or cerebral spinal fluid obtained by spinal taps. The new study may lay the foundation for less invasive techniques. "Using the skin instead of brain tissue for post-mortem diagnosis could be particularly helpful in cultures that discourage brain autopsy, such as China and India. These countries have the largest populations with the greatest number of patients, but brain autopsy is often not performed," said Zou.

"Further investigation is necessary to determine whether extra precautions should be taken during non-neurosurgeries of CJD , especially when surgical instruments will be reused," said Zou. Case Western Reserve School of Medicine researchers plan to further evaluate the potential risk of skin transmission through non-neurosurgeries, primarily using mouse models.

Explore further: Recombinant human prion protein inhibits prion propagation

More information: C.D. Orru el al., "Prion seeding activity and infectivity in skin samples from patients with sporadic Creutzfeldt-Jakob disease," Science Translational Medicine (2017). stm.sciencemag.org/lookup/doi/ … scitranslmed.aam7785

Related Stories

Recombinant human prion protein inhibits prion propagation

October 9, 2013
Case Western Reserve University researchers today published findings that point to a promising discovery for the treatment and prevention of prion diseases, rare neurodegenerative disorders that are always fatal. The researchers ...

Molecular link between Parkinson's disease and prion diseases

September 15, 2017
Parkinson's disease and prion diseases are very different as regards both origins and course. Nonetheless, a research group of SISSA, headed by Professor Giuseppe Legname, has discovered an unexpected and important link between ...

Research could lead to blood test to detect Creutzfeldt-Jakob disease

December 21, 2016
The detection of prions in the blood of patients with variant Creutzfeldt-Jakob disease could lead to a noninvasive diagnosis prior to symptoms and a way to identify prion contamination of the donated blood supply, according ...

Small loop in human prion protein prevents chronic wasting disease

February 23, 2015
Chronic wasting disease (CWD)—an infectious disease caused by prions—affects North American elk and deer, but has not been observed in humans. Using a mouse model that expresses an altered form of the normal human prion ...

Mutant prion protein could help reveal neurodegenerative disease mechanisms

November 23, 2016
For the first time, scientists have isolated a mutated prion protein that can multiply in the lab but not in living animals, according to a PLOS Pathogens study. The mutant prion provides new insights into the mechanisms ...

Prion disease detected soon after infection and in surprising place in mouse brains

September 22, 2015
Prion diseases—incurable, ultimately fatal, transmissible neurodegenerative disorders of mammals—are believed to develop undetected in the brain over several years from infectious prion protein. In a new study, National ...

Recommended for you

Doctors may be able to enlist a mysterious enzyme to stop internal bleeding

August 14, 2018
Blood platelets are like the sand bags of the body. Got a cut? Platelets pile in to clog the hole and stop the bleeding.

Byproducts of 'junk DNA' implicated in cancer spread

August 14, 2018
The more scientists explore so-called "junk" DNA, the less the label seems to fit.

Artificial placenta created in the laboratory

August 14, 2018
In order to better understand important biological membranes, it is necessary to explore new methods. Researchers at Vienna University of Technology (Vienna) have succeeded in creating an artificial placental barrier on a ...

Using DeepMind's neural network learning system to diagnose eye diseases

August 14, 2018
Three institutions working together have applied DeepMind's neural network learning system to the task of discovering and diagnosing eye diseases. Moorfields Eye Hospital has been working with Google's DeepMind Health subsidiary ...

3-D printed biomaterials for bone tissue engineering

August 13, 2018
When skeletal defects are unable to heal on their own, bone tissue engineering (BTE), a developing field in orthopedics can combine materials science, tissue engineering and regenerative medicine to facilitate bone repair. ...

Artificial intelligence platform screens for acute neurological illnesses

August 13, 2018
An artificial intelligence platform designed to identify a broad range of acute neurological illnesses, such as stroke, hemorrhage, and hydrocephalus, was shown to identify disease in CT scans in 1.2 seconds, faster than ...

2 comments

Adjust slider to filter visible comments by rank

Display comments: newest first

Caliban
5 / 5 (1) Nov 22, 2017
Crikey.

One notes that the obvious isn't addressed at all:

Humans shed skin cells continuously, everywhere they go, all the time.

They form the majority of common household dust, and part of the dust present in the general environment, everywhere, and moreso with increasing proximity to population centers.

We breathe these particles in, via respiration, on a continuous basis.

No need to wait to come into contact with infected brain or organ tissue.
Nik_2213
5 / 5 (1) Nov 22, 2017
Cue a swab-test, please ??

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.