Can you catch Alzheimer’s disease? Fear has been growing that the illness might be capable of spreading via blood transfusions and surgical equipment, but it has been hard to find any evidence of this happening. Now a study has found that an Alzheimer’s protein can spread between mice that share a blood supply, causing brain degeneration.
We already know from prion diseases like Creutzfeldt-Jakob Disease (CJD) that misfolded proteins can spread brain diseases. Variant CJD can spread through meat products or blood transfusions infected with so-called prion proteins, for example.
Like CJD, Alzheimer’s also involves a misfolded protein called beta-amyloid. Plaques of this protein accumulate in the brains of people with the illness, although we still don’t know if the plaques cause the condition, or are merely a symptom.
There has been evidence that beta-amyloid may spread like prions. Around 50 years ago, many people with a growth disorder were treated with growth hormone taken from cadavers. Many of the recipients went on to develop CJD, as these cadavers turned out to be carrying prions. But decades later, it emerged in postmortems that some of these people had also developed Alzheimer’s plaques, despite being 51 or younger at the time.
The team behind this work raised the possibility that some medical or surgical procedures may pose a risk.
Now a study has found that, when a healthy mouse is conjoined with a mouse with Alzheimer’s plaques, it will eventually start to develop plaques of beta-amyloid protein in its own brain. When the plaques form in healthy mice this way, their brain tissue then starts dying.
This suggests that Alzheimer’s can indeed spread via the beta-amyloid protein in blood. “The protein can get into the brain from a connected mouse and cause neurodegeneration,” says Weihong Song at the University of British Columbia in Vancouver, who led the work.
Song’s team conducted their study on mice with a gene that makes the human version of beta-amyloid, because mice don’t naturally develop Alzheimer’s. This gene enabled mice to develop brain plaques similar to those seen in people, and to show the same pattern of neurodegeneration.
The team then surgically attached mice with this Alzheimer’s-like condition to healthy mice without the beta-amyloid gene, in a way that made them share a blood system.
At first, the healthy mice started to accumulate beta-amyloid in their brains. Within four months, the mice were also showing altered patterns of activity in brain regions key for learning and memory. It is the first time that beta-amyloid has been found to enter the blood and brain of another mouse and cause signs of Alzheimer’s disease, says Song.
“They somewhat convincingly show that it is possible to induce [the plaques] in mice just by connecting the circulation,” Gustaf Edgren at the Karolinska Institute in Stockholm, Sweden. “It strengthens the case that amyloid beta is infectious somehow – it may actually be a prion or act like a prion.”
These findings contradict a study earlier this year by Edgren and his colleagues, which tracked 2.1 million recipients of blood transfusions across Sweden and Denmark. They found that people who received blood from people with Alzheimer’s didn’t seem to be at any greater risk of developing the disease.
Edgren says that although his own study was very large, there’s still a chance it did not run long enough to catch evidence that Alzheimer’s proteins might be transmissible. “We only have follow-up for 25 years,” he says. “It could take a long time [for the disease to develop], or there could not be enough data. A lot of researchers fear that it’s an infectious protein.”
Song’s team say it is too soon to draw conclusions from their findings. Stitching mice together is not a situation that applies to people, says Edgren.
Mathias Jucker at the German Center for Neurodegenerative Diseases in Tübingen doesn’t think the study shows that Alzheimer’s is a transmissible disease. And the team have not yet looked at the behaviour of the mice to see if they show signs of the cognitive decline characteristic of Alzheimer’s.
In the meantime, Song thinks researchers and doctors should pay more attention to beta-amyloid in the blood, which could potentially be used to diagnose the disease. One of the reasons it has been difficult to treat Alzheimer’s is the difficulty of designing drugs that can cross the brain’s protective barrier. It may be easier to target the protein in the bloodstream, which could have knock-on effects for the brain, says Song.
Journal reference: Molecular Psychiatry, DOI: 10.1038/mp.2017.204
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