Kurt Giles 03/15/09
March 16, 2009
Prion diseases have a long and complex history, replete with findings that couldn’t be explained
by the theories available at the time, and colorful characters working in the field. The term
“prion”, from the words “proteinaceous” and “infectious”, was only coined 25 years ago, but the
diseases they cause have been known for nearly 300 years.
The prototypic prion disease is called scrapie and affects sheep and goats. It was first reported
in Europe in the 18
century. One of the more obvious symptoms is in the animals trying to
relieve an apparent intense irritation by scratching against fence posts, hence the name.
In the early 20
century two German neurologists, Creutzfeldt and Jakob independently
identified a distinct brain pathology from patients that had died of an unusual neurodegenerative
disease, which now bears their names.
Prion diseases are also called transmissible spongiform encephalopathies (TSEs) which reflects
two important points: i) they are transmissible, i.e. infectious, and ii) they result in a severe
vacuolation, or “sponge-like” appearance in the brains of infected animals.
Prion diseases are best characterized in humans, sheep, cows and deer, but have also been
shown to infect apes, monkeys, mink, cats and other species.
Human prion diseases
Prion diseases can have one of three etiologies:
By far the most common form of Creuzfeldt-Jakob disease (CJD) has no apparent
origin. Worldwide there are 1-3 cases per million population per year, implying an approximately
1 in 10,000 lifetime chance of getting CJD.
More than 20 mutations in the prion protein (PrP) gene have been identified which
lead to an increased incidence of prion diseases, however, these still represent only about 10%
of cases seen. Whilst generally grouped under the heading of familial CJD, certain mutations
can give rise to specific disease phenotypes which are recognized as diseases in their own
right, such as fatal familial insomnia and Gerstmann-Stäussler-Scheinker syndrome.