Misfolded proteins may make dementia transmissible, scientists suggest: ScienceAlert

We have known since the 1980s that certain proteins behave like pathogens if they are not folded correctly.

These self-replicating molecular troublemakers, called prions, can cause brain tissue get worseas seen in mad cow disease and its human counterpart, Creutzfeldt-Jakob disease.

Over the past few decades, some intriguing studies have suggested that something similar may be happening in dementia.

The sticky clumps of amyloid beta protein found in the brains of people with Alzheimer’s disease can behave like prions and even spread to other people in very rare circumstances involving medical procedures.

Prion diseases are not transmitted through direct human-to-human contact. But prions can pass from cows to humans through the consumption of contaminated meat, and kuru—a neurodegenerative prion disease found in Papua New Guinea—was once spread through the ceremonial practice of eating the brains of deceased relatives.

Likewise, if Alzheimer’s disease can be transmitted through a misfolded protein, it wouldn’t be possible to catch it just by spending time with someone with the disease, the researchers say.

But a small number of historical cases and a few animal studies have raised concerns that unsuspecting patients could be infected with dangerous Alzheimer’s proteins during neurosurgery if the same tools are used on multiple patients.

Patients can also be exposed when they receive a tissue transplant from a person with misfolded amyloid beta. In either case, the effect won’t be seen until decades later because the protein takes a long time to replicate.

The first whispers of this idea were heard in 2006, when researchers implanted transgenic mice with brain tissue from people who had died of dementia. These mice developed the classic amyloid beta plaque seen in people with Alzheimer’s disease, while the control group did not.

In this experiment, the rate of plaque development is proportional to the amount of beta amyloid in the brain tissue and the time required for incubation. These are “patterns you would expect to see if the extracts caused the plaques,” the researchers wrote.

Synthetic amyloid beta injected into the brains of mice had a similar, though weaker, effect.

However, it wasn’t until 2015 that the concept of ‘contagious’ dementia started making headlines.

In a small study published in Natureresearchers examined the brain tissue of eight young adults who died of Creutzfeldt-Jakob disease.

Some 30-40 years earlier, as children, they had been injected with growth hormones from the pituitary glands of human cadavers to treat their short stature – and were inadvertently infected with the misfolded protein that causes Creutzfeldt-Jakob disease .

Four of these adults also had significant accumulation of amyloid beta in their brains.

This type of plaque is usually only seen in older people with moderate to severe Alzheimer’s disease and was a surprising finding for people who died so young.

This raised the possibility that the cadaveric injections seeded the people with amyloid-beta proteins, which turned into larger plaque deposits later in life.

The use of cadaver-derived growth hormone injections was stopped in 1985 when researchers realized that a small number of children received contaminated samples and developed Creutzfeldt-Jakob disease.

Three decades later, researchers tracked down archival samples of the original injections and confirmed that they contained amyloid beta.

They injected these old samples into the brains of young mice and found that they developed amyloid plaques and an associated brain bleeding condition called cerebral amyloid angiopathy.

Another study published in 2018 found that eight people who developed cerebral amyloid angiopathy under the age of 60 had undergone brain surgery as children or teenagers.

“These findings raise the possibility that amyloid-beta pathology may be transmitted, as is prion disease, by neurosurgical procedures,” the researchers concluded.

Earlier this year, in September, a large population-based study from Denmark and Sweden found that people who received blood transfusions from people who later developed a brain hemorrhage were more likely to develop a brain hemorrhage themselves. The study “may suggest a transfusion-transmitted agent,” the researchers reported.

This line of research raises the specter of transmissible dementia, which can pass from older to younger people if the same surgical tools are used.

This is troubling because common sterilization techniques, such as boiling, immersing in formaldehyde or drying, do not seem to affect amyloid beta, the sticky protein seen to clog the brains of people with Alzheimer’s disease.

However, neurosurgery for children is usually performed in children’s hospitals, where the instruments used have likely never been near an Alzheimer’s patient.

The more we understand about Alzheimer’s, the better we can treat it, but we’ve been burned before by amyloid beta research that looked promising but failed to pay off. And the evidence is still inconclusive.

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