Creutzfeldt-Jakob disease: prion protein misfolding
Creutzfeldt-Jakob disease (CJD) is a rare, rapidly progressive dementia caused by a prion, an infectious protein in an abnormally folded form.
Remember
A misfolded prion protein makes normal prion protein misfold in the same way, so CJD is a dementia that worsens over months, with sponge-like (spongiform) change in the brain and no effective treatment.
Memory aid
One bent paperclip bends the next
It pictures how one misfolded prion protein makes the next normal copy misfold, so the damage keeps spreading.
CJD is a prion disease, and a prion is an infectious protein. In health, the cellular prion protein sits on the surface of neurones (nerve cells). In CJD an abnormally folded version of that same protein appears. The misfolded form makes other normal copies refold into the abnormal shape, a bit like a chain reaction, so the problem spreads and accumulates.
As the misfolded protein builds up, neurones are lost. Down the microscope the brain tissue also develops many small empty spaces (vacuoles) that give it a sponge-like look, called spongiform change.
The disease is described as transmissible (it can pass between individuals), for example through transplanted tissue or contaminated neurosurgical instruments (those used in surgery on the nervous system), although most cases are sporadic (arise without a known cause). CJD can also be variant, linked to eating beef from cattle with bovine spongiform encephalopathy (BSE, also called mad cow disease), or inherited.
The clinical picture is memory loss, personality change and problems with balance, vision and speech, often with myoclonus (sudden involuntary muscle jerks) and ataxia (unsteady, uncoordinated movement). There is no effective treatment, and most patients die within a year of diagnosis.
The key exam contrast with the common dementias is time. Alzheimer's disease evolves over years, whereas CJD evolves over months.
Key facts
- Cause
- an infectious prion protein that has misfolded and converts normal prion protein.
- Pathology
- spongiform change (sponge-like holes in brain tissue) with loss of neurones.
- Clinical picture
- a rapidly progressive dementia with personality change, often with myoclonus and ataxia.
- Forms
- sporadic, variant (linked to BSE) and inherited, plus rare spread between people through transplanted tissue or contaminated neurosurgical instruments.
- Outlook
- no effective treatment, and most patients die within a year of diagnosis.
- Time course
- Alzheimer's disease evolves over years, whereas CJD evolves over months.
Exam traps
- CJD is not an autoimmune disease. Multiple sclerosis (where the immune system attacks the myelin sheath that insulates nerve fibres) is an autoimmune disorder, whereas CJD is caused by a misfolded protein.
- Plaques of beta-amyloid outside cells and tau tangles inside them define Alzheimer's disease (the commonest dementia), not CJD, which is a prion disease with a much faster course.
- Poor blood flow through narrowed small vessels causes vascular dementia, which tends to decline in steps, whereas CJD is caused by a misfolded protein.
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