Volume 2: Science
2. The Spongiform Encephalopathies - knowledge existing in 1986
Other neurodegenerative diseases
Huntington's disease (HD)
Alzheimer's disease (AD)
Parkinson's disease
Summary

2.39 By 1986 knowledge also existed about other degenerative diseases of the nervous system which, like CJD, are characterised by progressive dementia and neurological symptoms, including behavioural disturbance and ataxia, in later life. The best known of these conditions are Alzheimer's disease, Parkinson's disease and Huntington's disease. Although not TSEs, they are relevant to the discussion of TSEs as they are now known to share a common factor, namely the accumulation of insoluble and abnormal proteins in nerve cells. In Huntington's disease and in eight distinct forms of spinocerebellar ataxia, the abnormal proteins result from familial gene mutations inherited in the same way as in GSS. In some cases, a conformational change in the abnormal protein molecule has been demonstrated. A brief account is given below of the three most common of these neurodegenerative conditions. Each condition has to be considered as a possible diagnosis in suspected cases of CJD.

Huntington's disease (HD)

2.40 Huntington's disease (HD) is an inherited degenerative disease of the nervous system characterised by involuntary movements, ataxia, intellectual decline and progressive dementia. One in 18,000 people suffers from the disease. The major pathological feature of HD is degeneration of nerve cells in the brain.

2.41 Age of onset is between 35 and 45, which usually means that many sufferers reproduce and have passed on the gene to half of their offspring before they are aware of the disease. In 1983 the gene responsible for the disease was mapped to chromosome 4, opening up the possibility of using genetic markers linked to the disease gene for presymptomatic diagnosis. ¹ The gene was not characterised until 1993, and it was not until 1997 that aggregates of an insoluble mutant protein were demonstrated in neurons in degenerating brain. ²

Alzheimer's disease (AD)

2.42 Alzheimer's disease (AD) is the major form of pre-senile or senile dementia. It affects 1 in 20 people over the age of 65. AD is characterised by loss of nerve cells and abnormal brain activity, particularly in areas controlling intellectual properties.

2.43 By 1986 similarities between AD and CJD had been noted, ³ including the fact that both are familial in a small proportion of cases. ⁴ Both AD and CJD patients can suffer from twitching muscular movements and changes in the electrical activity of the brain. In one transmission study documented in 1982, primates were inoculated with brain tissue from patients with confirmed Alzheimer's disease. The animals developed a spongiform encephalopathy that was indistinguishable from CJD. However, other attempts to transmit AD have been unsuccessful. ⁵

2.44 More recently, neuropathological observations, supported by genetic and biochemical studies, have indicated a central role for abnormal protein deposits in the pathogenesis of Alzheimer's disease. ⁶

Parkinson's disease

2.45 Parkinson's disease is a common progressive degenerative disease of the nervous system starting late in life, and is characterised by tremors and rigidity. The major pathological features are loss of nerve cells in specific areas of the brain, and a deficiency in the neurotransmitter, dopamine. ⁷ The disease affects 2 in every 1,000 people, a small proportion of whom are familial cases.

2.46 In the early 1980s it had been suggested by several groups that the disease might be the result of an acute viral infection, or an ongoing slow infection of the nervous system in a small percentage of the cases. ⁸ However, by 1986, despite many efforts, no virus had been recovered from Parkinson's disease, and no transmission to animals had been reported.

2.47 Since 1986 it has been shown that several different gene mutations are involved in the disease, with each gene producing abnormal aggregates of proteins in nerve cells. ⁹

Summary

2.48 By 1986 several TSEs in both animals and humans were recognised. These progressive, degenerative diseases of the nervous system were known to share certain distinctive features including long incubation periods and clinical signs of neurological damage such as ataxia, spongy degeneration of the brain and, in some cases, deposits of amyloid in and around nerve cells. All TSEs are transmissible, both naturally and experimentally. By 1986 it was known that other neurodegenerative diseases, such as Alzheimer's and Parkinson's disease, were heritable in a small proportion of cases. But among neurodegenerative diseases only the TSEs had been shown to be capable of transmission by infection and by inheritance. It was later shown that the feature common to TSEs and these other forms of neurodegenerative disease is the presence of aggregates of insoluble protein associated with degenerating nerve cells. This implies similar mechanisms of cell injury and death in the central nervous system.