A misfolded protein that teaches its neighbours to misfold
Creutzfeldt–Jakob disease has no germ in the usual sense. A misshapen prion protein bends healthy copies into its own faulty form, a chain reaction that riddles the brain with tiny holes. It strikes about one person per million each year, and roughly 70 percent die within a year of diagnosis.
First described in 1920, the illness was named in 1922 by Walther Spielmeyer after two German neurologists, Hans Gerhard Creutzfeldt and Alfons Maria Jakob. It usually begins with fast-moving dementia, memory loss and personality change, followed by trouble with balance, speech and walking. Jerky muscle movements appear in about 90 percent of patients. Most die around six months after symptoms start, often from pneumonia once the cough reflex fails, though about 15 percent live two years or more.
The culprit is a protein normally found in nerve cells. When its structure flips from spiral coils into flat pleated sheets, it resists being broken down and converts other copies, so the faulty molecules multiply exponentially and kill neurons. Under a microscope the damaged tissue looks like a sponge, hence the family name, transmissible spongiform encephalopathies. Different folded shapes, called strains, seem to explain why subtypes behave differently, and a common variation at codon 129 of the PRNP gene affects who is susceptible.
Most cases have no known cause: roughly 85 percent are sporadic, perhaps linked to ageing cellular machinery, which fits a typical onset near 60. Another 10 to 15 percent are inherited. A small share came from medical procedures such as corneal or dural grafts and growth hormone taken from human pituitary glands, since replaced by a synthetic version. A variant form was linked to eating beef from cattle with mad cow disease. Prions shrug off routine sterilisation, so health agencies advise destroying instruments used on high-risk tissue or treating them with combined heat and chemicals.
Diagnosis once relied on excluding everything else. MRI scans can show a telltale ribbon of bright signal along the cortex, with a reported 91 percent sensitivity early in rapid dementia. The real-time quaking-induced conversion test, which amplifies traces of the misfolded protein, now sits at the centre, with second-generation versions reaching near-perfect specificity on spinal fluid. No cure exists; care focuses on easing pain and involuntary movements.
Source: Creutzfeldt–Jakob disease
