Creutzfeldt-Jakob Disease (CJD)

Creutzfeldt Jakob Disease (CJD) is a rare and invariably fatal neurodegenerative disease. Onset of CJD is marked by rapidly progressing dementia, loss of motor control, blindness and inevitably, death. In other words, by the time you notice the symptoms, it’s probably already too late. The majority of patients die within a year of initial infection.

Although there are still a few holdouts, the vast majority of the scientific community agrees that the causative agent of CJD is a prion.

Some of the alternative theories involve viroids, which are basically very tiny, bare nucleic acid particles that act like a virus in some cases. Unfortunately for these theorists, it’s been shown that the infectious agent of CJD can survive numerous conditions which would destroy viroids. There are others still who stipulate the involvement of some kind of virus, although most techniques used to kill viroids also would kill viruses.

Thus, although there are dissenters, it is more or less proven that the infectious agent of CJD is a prion.

This sets CJD apart from almost all other diseases in that prions (unlike bacteria, viruses, fungi, or many other infections agents) lack genes (Ingram, 2013). Prion diseases are, to the best of our knowledge, fairly rare. Most prion diseases are classified as Transmissible Spongiform Encephalopathies (TSEs), which means:

1) They can be transmitted between hosts

2) They cause infected tissues to become spongy

3) They effect the brain and central nervous system

In the case of CJD, the prion forms from an otherwise normal protein called “prion protein” or PRNP (yes, they were that unoriginal).  PRNP occurs naturally in our bodies, and functions in the central nervous system. When PRNP misfolds, however, it becomes a true “prion”. This prion is then capable of converting other normal proteins in the cell into versions of itself, which then continue the chain reaction (Lloyd, 2011).

The initial misfold can happen if there are certain mutations in the protein which make it more likely to misfold. Because these mutations can be inherited, it is possible to be genetically predisposed to develop CJD.  

In the case of a CJD infection, an already misfolded version of the protein can find its way into the body from brain surgery or from food infected with the prion. The latter case is what happened during the Mad Cow Disease scare in the late 90s and early 2000s. Mad Cow  is the colloquial term for Bovine Spongiform Encephalopathy. That’s right, it’s a TSE and it occurs in cows. It turned out that humans who ate beef contaminated with meat from a “Mad Cow” could develop symptoms of variant CJD.  The bovine version of the protein was able to cause the change in human proteins!

Normal Prion Protein and Disease State Prion Protein
Fig 1. Normal Prion Protein (PRNP) compared to disease state Prion Protein  [Mayo Clinic, via Google Images]

Eventually the prions will start to clump together, and symptoms of the disease are arguably the result of both the loss of the normal version of the protein and the aggregation of these prion clumps which can kill neurons in which they accumulate (NIH; NINDS, 2014).

Fig 2. The opening of vacuoles in brain matter infected with prions. The image depicts bovine tissue, but this formation of spongy tissue is common to all TSEs [USDA via Google Images]
Fig 2. The opening of vacuoles in brain matter infected with prions. The image depicts bovine tissue, but this formation of spongy tissue is common to all TSEs [USDA via Google Images]

There are three forms of CJD;

→ Sporadic CJD (sCJD): In this form, the disease arises despite the individual having no risk factors for CJD. This accounts for the majority of CJD cases, and encompases variant CJD (vCJD), which is the form of CJD associated with the Mad Cow Disease scare in the late 90s to 2000s (Collinge, 1990).

→ Hereditary CJD: In this form, the disease arises in an individual bearing a mutation in PRNP associated with CJD. This form is responsible for ~10% of cases.

→ Acquired CJD: In this form, the disease is passed from one individual to another via contact with contaminated brain matter. This is exceedingly rare and represents less than 1% of CJD cases

Although it is rare (about 300 cases in the US each year), CJD is always fatal and current treatment options are aimed at easing the pain of symptoms. There are a few recent studies which attempt to make our normal PRNP resistant to conversion by prions (Kong et al. 2013), but they are a long ways off from a clinical application. Additionally, there is evidence that there is a correlation between CJD and other neurodegenerative diseases such as Alzheimer’s (Armstrong 2001). For these reasons, research into CJD and other prion diseases is of great importance.

For further reading see…

Annotated Bibliography

EDITED 05-08-14: Added the answers to most of the questions I received in comments. Thanks to everyone who helped make the title page more understandable!

9 Replies to “Creutzfeldt-Jakob Disease (CJD)”

  1. Not a bad title page, but I think it could be improved with some changes. Instead of jumping into the cause of the disease, it might be a good idea to list some of the symptoms/characteristics first. Yes, you say it is a neurodegenerative disease, but how does this play out?

    Also you mention that “Although there are still a few holdouts, the vast majority of the scientific community agrees that the causative agent of CJD is a prion.” What are some of the other theories out there about its cause?

    I could understand your explanation of how a prion induces other proteins to misfold and become prions and thus the disease propagates, but what I am confused about is how does this start? Is the prion precursor a naturally occurring protein in our bodies or was it transferred to humans at some point in the past?

    1. Hey Hudson, thanks for the feedback. I was thinking about including more of the symptoms and how the disease progresses and such. I think I’ll add those in. As for the alternate theories, I mention them because they are out there, but they aren’t quite worth diverting or confusing readers of the title page, given how little support there is for them. Some people propose a novel type of virus, although it has been shown that the causative agent of CJD does not need nucleic acids to reproduce. I wanted to mention that there were other theories, but the agreement on the prion theory is almost 100%.

      I can see where the confusion about prion propagation might arise. PRNP, as mentioned, already has a cellular function. It is a membrane protein primarily in the CNS. If a copy of PRNP misfolds (sometimes this happens due to a mutation which makes it prone to misfolding, which would be the case with familial CJD). Other times, the prion protein can simply misfold by chance. Then, as is the case with transmitted cases of CJD, the patient’s brain can be infected by copies of the already misfolded PRNP from another person or even from other species. Mad Cow in cattle can sometimes be transferred to humans where we call it variant CJD (vCJD).

      Again, thanks for the comments. I’ll have to go back and make sure the main page is more clear on anything you had questions about.

  2. I appreciate the bits of humor throughout this. How many people does CJD affect? Are scientists exploring any new treatment options?

  3. Thanks Julia, that’s an excellent question. Part of the reason why CJD gets so little research money (hence, why we know so little about it) is because it only affects about 300 people in the US each year. It’s a fairly rare disease, and most of the cases are sporadic CJD, so the patients aren’t really even being watched for possible symptoms. Since more than 90% of cases result in death in under a year, it is probably more prevalent than we can confirm.

    Right now, it’s very hard to look at treatment options because the researchers’ grasp of the ways that prions work is not the best. It’s been getting much better over the past few years, but we are still unsure precisely how CJD even works. So, since it progresses so fast, it makes it pretty hard to do tests or trials. The first step, or rather the next step, is to learn more about exactly how this prion and the clumps it forms, causes all of this nerve death. There are still some missing pieces.

  4. Very good start! Your title page was very easy to navigate and you did a great job explaining the onset of prion diseases in layman’s terms as well as presenting the knowledge that is currently available regarding CJD. However, I feel that it may be helpful to develop the background a little more. That is, considering the rich historical context of the disease, it may be interesting to start off by mentioning that information as well as describing its origin and when it first appeared in association with Mad Cow. Also, it may be useful to the reader to describe the signs and symptoms associated with the disease before jumping into all of the science.

    Lastly, it may be interesting to briefly mention the treatment as well as current research that is surrounding drug therapy, if any. I look forward to learning more!

    1. Thanks Radhika. There have been a few people asking for more on symptoms and all that. One of the papers I just read for this project talked a little bit about treatment. There are some advances being made, but as I mentioned, the community still has a fairly tentative understanding of the whole picture, and is still working towards a good target for drugs.

  5. This is a very informative and well written introduction to your disease. I do like that you immediately differentiate this disease from others by making sure that the reader understands that the infectious agent is a molecule and not an organism of some kind. On that note, I do have one question, which is this: you mentioned in the first paragraph that there are a few hold outs that have different theories about the disease, and I was wondering if you knew anything about the specifics of these theories, though I realize some of them are likely a little strange.

    1. Evan, thanks for the comment. Yes, some of the alternative theories (although at this point they are more on the level of conspiracies) involve viroids, which are basically very tiny, bare nucleic acid that acts like a virus in some cases. Unfortunately for these theorists, it’s been shown that the infectious agent of CJD can survive nuclease digestion and very high temperatures which would denature DNA and certainly RNA.

      There are others still who stipulate some kind of virus. Nonetheless, it has been shown in vivo that the misfolded version of PRNP can convert the normal version, and that this infection causes the TSE-like symptoms and phenotypes.

      So, the alternative theories aren’t all that strange, per se, but they are essentially disproven. This highlights one of my favorite parts of the CJD story. Because prions were and still are such strange and unorthodox infectious agents, there is bound to be some resistance in the community. It underscores the human nature of science. There are all kinds of emotions concerning who discovered what first and whose research disproves what. Overall, since prion science is a fairly young field, it is bound to be messy and tied up with ego as the basic rules and theories are solidified, which is the period we are starting to see happen now.

  6. The initial presentation of CJD in the introductory portion of this post is written coherently and the terminology used are very specific and utilized efficiently to get their meaning across. From there, the post remained consistent in regards to those terms by mentioning them again and explaining further. The small amount of humor made it less robotic and slightly more humane and free flowing. The diagrams connected to the information were placed appropriately and served it’s purpose of clarifying the data even further.
    It’s slightly unnerving to hear of this detrimental disease and not know of any concrete cures or treatments but the current information is enough to at least inform of what might happen and why.
    A very interesting read.

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