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Investigating the Biomechanics of Disease
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Creutzfeldt-Jakob Disease CJD


Sporadic CJD

CJD was described in the 1920's and is a neurodegenerative disease that normally is a disease of the elderly, which causes dementia in an aggressive manner in many cases, with 70% of people affected dying within six months of the first major symptoms and as a general rule one can say that if an individual who is suspected of having CJD is still able to talk and walk after one year then that individual is unlikely to have CJD. Sporadic CJD represents up to 90% of human CJD cases, and sporadic CJD occurs at a fairly consistent rate of approximately one per million worldwide. The peak occurrence of sporadic CJD is between 60-65 years of age and the range is usually between 45-75 years, and it is very rare for an individual younger than 30 years old to be affected with CJD.

The quick progression of the dementia is accompanied by other neurological aspects such as; cerebellar ataxia (loss of control of bodily movements) and myoclonus (involuntary jerks and twitching of muscles); there is a rapid loss of speech and the ability to walk. There can also be, in rare cases, visual disturbances culminating into cortical blindness. There is a deposition of PrPSc forming aggregates, neuronal loss, astrocytic gliosis, and the spongiform change or vacuolar formation.

There does seem to be some genetic biased with regards sporadic CJD which centre upon residue 129 of the prion protein. A common polymorphism (change in type of amino acid) that occurs at this position is that there can be either a methionine (M) or a valine (V) at this position. In Caucasians approximately 38% are homozygous for methionine (MM), 51% are heterozygous having both a valine and methionine (MV or VM), and 11% are homozygous for valine (VV). In sporadic CJD a larger majority, around 70%, of people affected are homozygous for methionine at residue 129.

Familial or genetic CJD

Although the distribution of CJD is roughly evenly distributed, there were found to be little clusters, for example, there where Libyan Jews who had immigrated to Israel who were thirty times more prone to CJD than the rest of the Israeli population. It was found that these people had a mutation on codon 200 in the prion gene with glutamate (E) being replaced with a lysine (K) residue at position 200 on the prion protein, this is written E200K.

This and other similar mutations that are linked to genetic predisposition to develop CJD are listed below:
  1. Valine (V) replaced by Isoleucine (I) at position 180 (V180I)
  2. Glutamate (E) replaced by Lysine (K) at position 196 (E196K)
  3. Glutamate (E) replaced by Lysine (K) at position 200 (E200K)
  4. Valine (V) replaced by Isoleucine (I) at position 203 (V203I)
  5. Arginine (R) replaced by Histidine (H) at position 208 (R208H)
  6. Valine (V) replaced by Isoleucine (I) at position 210 (V210I)
  7. Glutamate (E) replaced by Glutamine (Q) at position 211 (E211Q)
  8. Methionine (M) replaced by Arginine (R) at position 232 (M232R)

There is also a linked pair of polymorphisms, one polymorphism is where an Aspartic Acid (D) amino acid is replaced by a Asparagine (N) at position 178 (D178N) and if this occurs when a Valine is at position 129 (V129), this leads to a predisposition for CJD.

There is also the deletion of two of the octapeptide repeats which can lead to dementia and CJD.

New "Variant" CJD (vCJD)

In the UK in 1995 two cases of CJD were reported in young teenagers, and this seems to be the start of a new "variant" CJD (vCJD) epidemic. The two cases were different from typical CJD, because of their ages but also because of the kuru-type plagues (florid plagues) that were present in their brains on autopsy, these types of plagues are present in only ~5% of cases in sporadic CJD. Over 140 cases of vCJD have been observed in the UK up to about 2004. There is a strong suggestion that there is a link with vCJD and BSE, and that the affected individuals have acquired vCJD by consuming beef from cattle that had BSE. All the people who have been identified as having vCJD so far have all been methionine homozygous at position 129 on the prion protein (PRNP gene).