Creutzfeldt-Jakob disease (CJD) is a rare and uniformly fatal neurodegenerative condition that causes rapid brain damage. It is caused by an abnormal protein called a prion, which accumulates in the brain and leads to irreversible damage to nerve cells.
Spontaneous Occurrences
The most common form of CJD is sporadic CJD, accounting for approximately 85% of all cases. In this form, normal prion proteins spontaneously misfold into the abnormal, disease-causing shape. The exact reason for this spontaneous change remains unknown, though it is hypothesized to involve the effects of aging on cellular machinery.
Sporadic CJD typically manifests later in life, with symptoms usually developing between the ages of 60 and 65, and a median age of onset around 62 years. This form is distinct because it is not linked to any external exposure or inherited genetic predisposition. It arises seemingly at random, affecting about one to two individuals per million globally each year.
Acquired Forms
CJD can also be acquired through external exposure to prions, leading to several distinct forms. One such form is variant CJD (vCJD), which is strongly linked to consuming meat products from cattle infected with bovine spongiform encephalopathy (BSE), commonly known as “mad cow disease”. This link was first recognized in the United Kingdom in 1996, where the majority of vCJD cases occurred following a large BSE outbreak in the late 1980s and early 1990s.
Iatrogenic CJD (iCJD) occurs due to accidental transmission during medical or surgical procedures. Historically, this included the use of human growth hormone derived from cadaveric pituitary glands, contaminated dura mater grafts used in brain surgery, and corneal transplants. Inadequately sterilized neurosurgical instruments have also been implicated. While these routes of transmission have been significantly reduced or eliminated through improved medical practices and screening procedures, they highlight the resilience of prions.
Kuru represents a historical acquired form of CJD, primarily observed among the Fore people of Papua New Guinea. This disease was transmitted through ritualistic funerary cannibalism, where brain tissue of deceased relatives was consumed. Women and children were disproportionately affected because they frequently consumed the brain, which contained high concentrations of infectious prions. The practice was discouraged in the 1960s, leading to a decline in cases, though the long incubation period, which could extend beyond 50 years, meant some cases continued to appear for decades.
Genetic Inheritance
Familial CJD is a form of the disease caused by an inherited genetic mutation in the prion protein gene (PRNP). This type accounts for 10-15% of all CJD cases. It follows an autosomal dominant inheritance pattern, meaning that only one copy of the mutated gene is sufficient to cause the disease.
Over 30 different mutations in the PRNP gene have been identified that can lead to familial forms of prion disease. These mutations predispose the normal prion protein to misfold into the pathogenic form over time. While this form is hereditary, new mutations can also occur spontaneously in the PRNP gene, which can then be passed down to future generations.
What Poses No Transmission Risk
Creutzfeldt-Jakob disease is not transmitted through typical daily interactions. Casual contact, such as touching, hugging, or kissing an affected individual, does not spread the disease. Likewise, airborne droplets from coughing or sneezing, or sexual contact, do not transmit CJD.
While variant CJD has been linked to rare cases of transmission through blood transfusions, classical CJD is generally not transmitted this way. Studies, including a 28-year lookback study in the United States, have found no evidence of sporadic CJD transmission via blood transfusions, suggesting the risk is minimal. Prions resist conventional sterilization methods, necessitating specific precautions in medical settings. However, this resistance does not imply a risk from casual everyday contact.