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The number of cases of Creutzfeldt-Jakob disease, a fatal human brain
disorder similar to ‘mad cow’ disease, has been seriously underestimated,
according to British researchers. The claim, based on a study of more than
1000 people who died of dementia, will renew public concern about the way
the government is monitoring the disease in the wake of the epidemic of
BSE in cattle.

CJD is one of a group of spongiform encephalopathies linked to a type
of protein known as a prion, which is abnormal in the brains of sufferers.
A few cases of the disease run in families that carry a defective gene.
Others arise by chance, and some have been blamed on medical treatments
where patients received brain tissues from an infected donor. The disease
may take decades to incubate, but once symptoms appear sufferers rapidly
lose their mental faculties, their sight and control of their limbs. Most
die within six months.

According to most estimates, CJD affects about one person in a million
every year. But now scientists at the Medical Research Council’s neuropathology
unit at Runwell Hospital in Essex, and colleagues at the pharmaceuticals
company SmithKline Beecham and Charing Cross Hospital in London are challenging
this view. They studied more than 1000 case records of people who had died
from various types of dementia over the past 25 years. Of these, 19 were
shown by laboratory studies to have died of CJD; their brains had the characteristic
spongy appearance of the disease and an excess of the abnormal prion protein.
But according to these patients’ notes, only 11 of them had been diagnosed
as having CJD. The remaining eight had been labelled as having other diseases.

Six of the eight missed cases had been mistakenly diagnosed as having
Alzheimer’s disease. Their symptoms were not typical of CJD: they had lived
for about three years after their dementia was diagnosed, and they had fewer
signs of damaged coordination. Gareth Roberts, a member of the team, says
the results indicate that CJD is ‘clearly’ more common than previously supposed.
The team is presenting its findings early next week at a meeting in the
US on Alzheimer’s disease.

The findings raise two important questions. First, are many cases of
CJD being mistaken for other types of dementia because too few postmortem
examinations are done? ‘Our crusade has been to say that people ought to
do more postmortems,’ says Clive Bruton, another member of the team. Secondly,
do the classic symptoms of CJD represent the whole picture of the disease
or are they only part of the story? Roberts believes that the presence of
the abnormal prion protein is the only sure indicator of CJD.

If this is correct, then scientists may need to rethink the official
figures on the disease. ‘The epidemiology is probably a mess,’ says Roberts.
Å®ÉúСÊÓƵs in Edinburgh, who began a nationwide epidemiological study of
CJD following the outbreak of BSE in British cattle, were unavailable for
comment before New Å®ÉúСÊÓƵ went to press.

Other researchers argue that it is not surprising that a few cases
of CJD are attributed to other causes. ‘This is a rare disease,’ says John
Collinge, who studies prion diseases at St Mary’s Hospital Medical School
in London. ‘You are not talking about thousands of people but a few cases.’

In a separate development, Collinge and his colleagues have uncovered
new clues to the mechanisms of CJD. The normal form of the prion protein
may be essential to allow nerve impulses to cross synapses properly. In
mice that are unable to make their own prion protein, brain tissue shows
‘marked abnormalities’ in synaptic function, says Collinge. In particular,
the uptake of the neurotransmitter GABA by its receptors is altered.

In CJD and other prion diseases, says Collinge, it seems likely that
the build-up of the abnormal prion protein destroys the function of the
normal one, producing similar effects to those seen in the mice. ‘This is
a real handle on what the protein does,’ says Collinge. The work, described
in this week’s Nature, may even allow them to design drugs that would bind
to the abnormal protein, slowing its accumulation.