Variant Creutzfeldt-Jakob Disease

What Is Variant Creutzfeldt-Jakob Disease?

Creutzfeldt-Jakob disease (CJD), a rare degenerative condition reported in 1922, is a subtype of prion disease caused by the misfolded prion protein. Generally, CJD is divided into three types: sporadic CJD, hereditary CJD, and acquired CJD, among which variant creutzfeldt-Jakob disease (vCJD) is a kind of acquired CJD caused by acquired infection from a non-human species.

vCJD, also referred to as human bovine spongiform encephalopathy or human mad cow disease, is a fatal brain disease lately identified in 1996. Unlike classic CJD that mainly affects elder individuals, vCJD tends to be infected among younger populations around the age of 28. The early manifestations of the vCJD are psychiatric problems, memory loss, and dyskinesia, which rapidly advances presenting symptoms such as poor coordination ability, dementia, and involuntary movement. It takes about 14 months from the onset of symptoms to death.

Main Causes of Variant Creutzfeldt-Jakob Disease

It should be noted that the vCJD cannot be diagnosed when the patient is alive. The main diagnostic method is to perform a post-mortem biopsy after death to analyze whether prions are present in the brain. As a type of acquired CJD, vCJD can be caused by direct or indirect exposure to infectious prions, such as:

Bovine spongiform encephalopathy. The first vCJD reported in 1996 in the UK was caused by eating contaminated beef infected with bovine spongiform encephalopathy. Therefore, dietary exposure to the bovine spongiform encephalopathy agent is the most likely cause of the vCJD.
Blood transmission. It has been demonstrated that the misfolded prion protein might be detected in individuals with vCJD. Although it is extremely rare, blood pathways such as blood transfusions, blood products, contaminated surgical instruments all are risks of vCJD.
Other causes. vCJD can be caused by the injection of growth hormone directly from the human pituitary gland or neural tissue contamination.

Role of Prion in Variant Creutzfeldt-Jakob Disease Pathogenetics

As with other prion diseases, vCJD is also caused by abnormally folded prion protein (PrP). Normally, PrP is a protease-sensitive protein with a highly conserved sequence and a mainly α-helical structure, which is widely expressed throughout the body, especially abundantly expressed in the nervous system. The pathogenic PrP in bovine spongiform encephalopathy is a misfolded protein with both β-sheets and α-helixes, exhibiting high resistance to protease.

Fig.1 Normal and pathogenic form of the prion protein. (Clark, 2016)

Once the body has ingested contaminated beef bovine spongiform encephalopathy, the abnormal PrP can be transported across the intestinal epithelium by M-cells, then circulate in the blood and enter the central nervous system. Moreover, the pathogenic PrP also can bind to normal PrP and convert the normal PrP structure into pathogenic PrP. Thus, more and more pathogenic PrPs accumulate in the neurons due to protease resistance. The continuous accumulation causes the neuron to rupture and form space, resulting in vacuolation of nerve tissue and spongiform change in the brain.

Fig.2 Characteristic feature of vCJD neuropathology and model of the pathogenesis of vCJD. (Hilton, 2006)