Alzheimer’s Disease, Prion Diseases Share Similarities
Photo: Marleen Van Den Neste
Fatal brain disorders called prion diseases might provide insight into the cause of Alzheimer’s disease, said Dr. John Collinge at a recent Wednesday Afternoon Lecture Series talk in Lipsett Amphitheater.
“There are more and more similarities between what we see in prion disease and what we’re seeing in Alzheimer’s disease,” said Collinge, professor of neurology at University College London (UCL), director of the United Kingdom Medical Council prion unit, director of the UCL Institute of Prion Diseases, director of the National Hospital for Neurology and Neurosurgery’s United Kingdom National Prion Clinic and visiting professor of neurology at Harvard Medical School.
A prion is an abnormal form of a naturally occurring protein that has the ability to catalyze the conversion of the normal form into the same abnormal form. Prions have been implicated in several diseases known as transmissible spongiform encephalopathies, which affect animals and humans, Collinge said. Over time, prions accumulate and damage the brain.
Symptoms of prion disease include changes in behavior, rapid onset of dementia and movement problems. Prion diseases are usually rapidly progressive and always fatal, according to the CDC. Most cases of prion disease occur randomly, Collinge explained. Certain host mutations can increase the risk of getting the disease.
The first prion disease shown to be transmissible from one person to another was kuru, a disease discovered among the Fore people of Papua New Guinea. In the 1950s, almost 2 percent of the population died from kuru annually. Collinge said it affected women and children of both sexes.
As a mark of respect, the Fore people consumed their deceased relatives’ brains at funerals. Although the practice had cultural significance, it also transmitted the fatal disease. Even though the feasts ended in 1959, when the link to kuru was established, the disease continued to appear decades later in patients who had been infected earlier.
“We’ve seen patients with incubation periods up to 60 years, which is quite extraordinary,” Collinge said.
One of the most common forms of prion disease is Creutzfeldt-Jakob disease (CJD). One type is classic, or sporadic CJD, which typically affects patients ages 65 years or older. Most patients die within 6 weeks of diagnosis. It doesn’t pass from person to person. There is no risk of acquiring CJD from contact.
Another type is variant CJD, which results when a person eats meat infected with bovine spongiform encephalopathy, also known as “mad cow disease.” Variant CJD typically affects patients under 30 years old.
Prion diseases can also be acquired from medical procedures, Collinge explained. Between 1958 and 1985, doctors in the U.K. gave human growth hormone (HGH) to treat almost 2,000 children with delayed growth problems. The HGH was taken from the pituitary glands of people who died.
In 1985, one patient treated with HGH from cadavers died from what’s called iatrogenic CJD. Evidently, some of the HGH that patient received came from a person who had prion disease. Although treatments using human-derived growth hormone stopped more than 30 years ago, Collinge still sees patients who develop iatrogenic CJD.
Photo: Credit Marleen Van Den Neste
In reviewing autopsy materials of patients who died long ago from iatrogenic CJD, Collinge found evidence of Alzheimer’s disease. Although the patients didn’t have Alzheimer’s symptoms, he worried that the “seeds” of harmful proteins associated with the disease could be transmitted during medical procedures involving human tissue, particularly tissue from the central nervous system.
Collinge found some of the HGH the children received in a medical archive and confirmed the hormone had Alzheimer’s proteins. Then, his lab injected the hormone into mice. Sure enough, there was “unequivocal evidence of seeding.”
There’s no risk of catching Alzheimer’s from a person with the condition—“the concern relates only to inoculation by medical procedures,” he clarified.
Doctors must continue epidemiological research to determine whether or not there’s a link between surgical procedures and Alzheimer’s disease. Until then, he advised physicians to consider the risks of transmission and sterilize or destroy contaminated surgical instruments.
Recently, Collinge and his lab began offering an experimental monoclonal antibody called PRN100 to patients with sporadic CJD. Mouse studies of PRN100 have been promising. Results have shown the antibody prevents abnormal proteins from attaching themselves to normal proteins and spreading. It’s too soon to say whether the drug will eventually be effective treating prion diseases in humans.
“It’s early yet, but I’m relieved we’ve gotten underway to test this drug in patients with this awful disease,” Collinge said.