Alzheimer's has long been recognized as a sporadic condition – influenced by factors such as age, genetics, and lifestyle – but scientists don't think that's the only way the disease emerges.
In recent years, researchers have suggested Alzheimer's may also spread through infection, which might somehow be transmitted like a pathogen, ultimately manifesting in the disease.
In a new report published in The Lancet, scientists review the evidence for one aspect of this theory, assessing how harmful amyloid-beta proteins associated with Alzheimer's might possibly be spread through blood transfusions.
"Blood transfusions are important and save many lives," says neurologist John Collinge from University College London.
"However, to ensure that they are as safe as they can possibly be, it's important that we thoroughly investigate any potential risks."
In 2015, a study provided the first real-world evidence that amyloid pathology might be transferable between humans through medical procedures, and subsequent research in 2016 found more evidence of the same thing.
In the years since, other studies have uncovered additional evidence.
A paper published in 2018 suggested contaminated surgical tools might transmit Alzheimer's proteins between patients, perhaps similarly to how infectious prions cause healthy proteins to become misfolded, harmful proteins.
In terms of blood transfusion risks, a turning point came in 2023, when a large population study from Denmark and Sweden found that people who had received blood transfusions from donors who later developed intracerebral hemorrhages were more likely themselves to develop recurrent brain bleeds years after.
One of the reasons that's significant is because spontaneous brain bleeds are a characteristic symptom of cerebral amyloid angiopathy (CAA) – a separate condition to Alzheimer's, but also associated with amyloid-beta proteins.
According to Collinge and team, the "most biologically plausible explanation" for what occurred is that incipient seeds of amyloid-beta – which hadn't yet developed into the CAA disease – were contained in the donors' blood, and were transmitted to the recipients during the blood transfusions.
Of course, we don't know for sure that's what happened, and the researchers are cautious to not over-claim.
But they argue that we know enough about the potential risks here to start protecting ourselves, in case blood-borne transmission of Alzheimer's pathology is more than just theory.
"The transmission of amyloid-beta pathology via transfused blood and blood products is a justifiable concern," the researchers write in their paper.
"We need to acknowledge that we do not have sufficient information to quantify the extent of the problem or the technologies that are needed to address key questions."
First up, the team says we need large-scale epidemiological analyses like the Scandinavian study – which studied over 1 million people – to further investigate whether more than just blood is being transferred during blood transfusions.
Additional safeguards could be extra monitoring of patients at greater risk (due to their need for repeated transfusions, for example), and a new system to see whether blood biomarkers for Alzheimer's can help identify blood donors who might be at risk of carrying amyloid-beta pathology.
The risks may largely be theoretical at this point, but the researchers say we know too well the dangers of not being prepared.
The UK Infected Blood Inquiry, released in 2024, examined the UK's infected blood scandal, which may have infected more than 30,000 patients between the 1970s and 1990s with contaminated blood, and is described as "the worst treatment disaster in the history of the National Health Service".
"The Infected Blood Inquiry provides a cautionary tale in waiting for absolute certainty before making decisions on patient safety," Collinge says.
"We also think it's important to be open and transparent about possible risks of amyloid-beta transmission, so that we can proactively mitigate any potential risk to patients."
Related: Prion-Like Brain Damage Can Occur Without Infectious Prions, Study Finds
While experts say the known risks are currently small, they agree we need to learn more about what could be happening here, while maintaining public confidence in the safety of blood transfusions.
"What this review does is identify an important gap in our knowledge," says Susan Kohlhaas, Executive Director of Research and Partnerships at Alzheimer's Research UK, who wasn't involved with the paper.
"The authors make the case for specific research to establish whether transmission through blood is occurring, who might be most at risk, and whether measures are needed to reduce that risk.
"At present, we simply don't have enough evidence to answer those questions, which is why this is important, and more research is needed."
The findings are reported in The Lancet.
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