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Health and Disease

A Review of Prion Diseases

Prion diseases, also referred to as transmissible spongiform encephalopathies (TSEs), are able to affect humans and animals and can be transmitted by the consumption of infected meat products. With approximately three hundred cases reported in the U.S. every year, prion diseases are a family of rare progressive neurodegenerative diseases and are identified by certain characteristics such as, changes in neuronal loss, and dysfunctioning inflammatory response. 

By Nara Ito

Published 2:42 PM EST, Wed March 24, 2021

Introduction

As suggested by the name, prion disease is ultimately caused by prions. Prions are abnormal, pathogenic agents, that can cause the abnormal folding of normal cellular proteins, called prion proteins. Prion proteins are found most abundantly on the surface of cells in the brain thus when having become abnormal, and clump together, can easily lead to brain damage and rapidly progressive and fatal conditions. 

About Prion Disease

The individual can develop prion disease sporadically, which is by chance, which occurs the most often; genetically, where the patient inherits prion disease however, fewer than 15% of people with prion disease have a family history of the disease or test positive for a genetic mutation associated with prion disease; and by contamination, by which in few cases people have developed prion disease after being exposed to infected human tissue amidst medical procedures, such as during a cornea or skin transplant and a few people have developed prion disease after undergoing brain surgery with contaminated instruments. A small number of people have also developed prion disease from eating meat contaminated with mad cow disease. 

Some types of prion disease would include: 

CJD (Creutzfeldt-Jakob Disease)

  •  Most cases of CJD are sporadic and tend to occur in those around age 60. Symptoms of CJD quickly lead to severe disability and death. In most cases, death occurs within a year.  

Variant CJD

  •  First capturing major public attention in the 90s after people in the UK developed this after eating meat from diseased cattle, this is an infectious type of the disease that is related to “mad cow disease.” Eating diseased meat may cause the disease in humans. This type of the disease usually affects younger people. 

Variably protease-sensitive prionopathy (VPSPr)

  • Similar to CJD but the proteins involved in pathogenesis are less sensitive to digestion. It is more likely to occur in individuals over the age of 70 who have a family history of dementia.  

The most common form of prion disease that affects humans is Creutzfeldt-Jakob disease (CJD). 

  • Creutzfeldt-Jakob is a degenerative brain disorder that leads to dementia and, ultimately, death.  Symptoms are similar to those of other dementia inducing brain disorders, such as Alzheimer’s disease.  Worldwide, about one to two cases of CJD are diagnosed per million people each year. 

General symptoms of CJD include: 

  • Rapidly developing dementia 
  • Difficulty walking and changes in gait 
  • Hallucinations 
  • Muscle stiffness 
  • Confusion 
  • Fatigue 
  • Difficulty speaking 
  • This abnormal accumulation of protein in the brain can cause memory impairment, personality changes, and difficulties with movement. 

The pattern of symptoms can vary depending on the type of Creutzfeldt-Jakob disease (CJD). 

In sporadic CJD, the neurological symptoms, affecting the CNS develop rapidly and worsen in the space of a few months. 

Initial neurological symptoms of sporadic CJD can include: 

  • difficulty walking caused by balance and coordination problems  
  • slurred speech  
  • numbness or pins and needles in different parts of the body  
  • dizziness  
  • vision problems, such as double vision and hallucinations 

Advanced neurological symptoms of all forms of CJD can include: 

  • loss of physical coordination, which can affect a wide range of functions, such as walking, speaking and balance
  • muscle twitches and spasms  
  • loss of bladder control and bowel control 
  • blindness 
  • swallowing difficulties 
  • loss of speech  
  • loss of voluntary movement 

In variant CJD, behavioural and psychological will usually develop first.  

Initial psychological symptoms of variant CJD can include: 

  • severe depression 
  • intense feelings of despair  
  • withdrawal  
  • anxiety 
  • irritability  
  • insomnia 

Advanced psychological symptoms of all forms of CJD include: 

  • loss of memory, which is often severe  
  • problems concentrating  
  • confusion  
  • feeling agitated  
  • aggressive behaviour  
  • loss of appetite, which can lead to weight loss  
  • paranoia   
  • unusual and inappropriate emotional responses 

Familial CJD has the same sort of pattern as sporadic CJD, but it often takes longer for the symptoms to progress, usually 2 years, rather than a few months. 

The pattern of iatrogenic CJD is unpredictable, as it depends on how a person became exposed to the infectious prion that caused CJD. 

The vast majority of CJD patients usually die within 1 year of illness onset. In about 85% of patients, CJD occurs as a sporadic disease with no recognizable pattern of transmission. A smaller proportion of patients (5% to 15%) develop CJD because of inherited mutations of the prion protein gene. 

Physicians suspect a diagnosis of CJD on the basis of the typical signs and symptoms and progression of the disease, including the presence of 14-3-3 protein in the cerebrospinal fluid however, as CJD is always fatal this must be confirmed with other means. 

Prion diseases are confirmed by taking a sample of brain tissue during a biopsy or after death. Healthcare providers, however, can do a number of tests before to help diagnose prion diseases such as CJD, or rule out other diseases with similar symptoms. 

The tests include: 

  • MRI scans of the brain 
  • Samples of fluid from the spinal cord 
  • Blood tests 
  • Neurologic and visual exams to check for nerve damage and vision loss 
  • Electroencephalograms 

Prion diseases can’t be cured, but certain medicines may help slow their progress. Besides sporadic onset, this disease can be prevented by properly cleaning and sterilizing medical equipment and tougher regulations governing the handling and feeding of cows. 

Nara Ito, Youth Medical Journal 2021

References

Prusiner S. B. (1991). Molecular biology of prion diseases. Science (New York, N.Y.), 252(5012), 1515–1522. https://doi.org/10.1126/science.1675487 

Prusiner, S. B. (1996). Molecular biology and pathogenesis of prion diseases. Trends in biochemical sciences, 21(12), 482-487. 

Prusiner, S. B. (1996, January). Molecular biology and genetics of prion diseases. In Cold Spring Harbor symposia on quantitative biology (Vol. 61, pp. 473-493). Cold Spring Harbor Laboratory Press. 

Clarke, A. R., Jackson, G. S., & Collinge, J. (2001). The molecular biology of prion propagation. Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences, 356(1406), 185-195. 

Weissmann, C. (1994). Molecular biology of prion diseases. Trends in cell biology, 4(1), 10-14. 

Sarnataro, D., Pepe, A., & Zurzolo, C. (2017). Cell biology of prion protein. Progress in molecular biology and translational science, 150, 57-82. 

Harris, D. A. (1999). Cellular biology of prion diseases. Clinical microbiology reviews, 12(3), 429-444. 

Collinge, J. (2005). Molecular neurology of prion disease. Journal of Neurology, Neurosurgery & Psychiatry, 76(7), 906-919. 

Wadsworth, J. D., & Collinge, J. (2011). Molecular pathology of human prion disease. Acta neuropathologica, 121(1), 69-77. 

Sigurdson, C. J., Bartz, J. C., & Glatzel, M. (2019). Cellular and molecular mechanisms of prion disease. Annual Review of Pathology: Mechanisms of Disease, 14, 497-516. 

Moore, R. A., Taubner, L. M., & Priola, S. A. (2009). Prion protein misfolding and disease. Current opinion in structural biology, 19(1), 14-22. 

Cohen, F. E. (1999). Protein misfolding and prion diseases. Journal of molecular biology, 293(2), 313-320. 

Nunziante, M., Gilch, S., & Schätzl, H. M. (2003). Prion diseases: from molecular biology to intervention strategies. Chembiochem, 4(12), 1268-1284. 

Horwich, A. L., & Weissman, J. S. (1997). Deadly conformations—protein misfolding in prion disease. Cell, 89(4), 499-510. 

Taraboulos, A., Raeber, A. J., Borchelt, D. R., Serban, D., & Prusiner, S. B. (1992). Synthesis and trafficking of prion proteins in cultured cells. Molecular biology of the cell, 3(8), 851-863. 

By Nara Ito

Nara Ito is a student from London, England. She is interested in neurology, immunology, and genetics

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