Blood transfusions could possibly transmit harmful brain proteins like amyloid-beta, a review suggested, and additional research and safety measures may be warranted.
"The risks of transfusion-related transmission of amyloid-beta pathology are currently undefined, and achieving clarity will take time," wrote John Collinge, MD, of University College London, and colleagues in The Lancet.
"Rigorous science will help find answers, but in the meantime, public health officials and blood transfusion services are faced with difficult decisions and urgently require further data on risk and access to feasible and accurate screening assays," they stated.
In their Lancet Viewpoint article, Collinge and co-authors reviewed evidence for transmitting amyloid-beta, a protein associated with Alzheimer's disease and cerebral amyloid angiopathy (CAA).
"The Viewpoint article arose from an international workshop we convened to review the evidence that amyloid-beta pathology might be transmissible by blood transfusion," Collinge said.
"This was in the light of a large Scandinavian epidemiological study suggestive of such a risk and the existing literature on iatrogenic transmission of amyloid-beta pathology from historical use of cadaver-derived pituitary growth hormone and dura mater," he told MedPage Today.
In 2023, an epidemiologic study in Sweden and Denmark suggested that a transfusion-transmissible agent was associated with some types of spontaneous intracerebral hemorrhage (ICH), which could reflect CAA.
Led by researchers at the Karolinska Institute in Stockholm, the retrospective study of over 1 million patients in two cohorts showed that recipients of red blood cell transfusions from donors who later had multiple ICHs had a significantly increased risk of spontaneous ICH themselves.
Epidemiologic studies like this have inherent limitations, including the fact that detailed phenotyping to confirm CAA is not possible, Collinge and colleagues acknowledged. "However, these findings are consistent with a factor associated with intracerebral hemorrhage risk being transferrable between donor and recipient, the most biologically plausible explanation being transmission of amyloid-beta seeds," they suggested.
"Seeded protein misfolding and aggregation are relevant to many neurodegenerative diseases," they wrote. "The archetype are prions: protein-only infectious agents that cause fatal neurodegenerative diseases including Creutzfeldt-Jakob disease."
Collinge and colleagues first reported human-to-human transmission of amyloid-beta pathology in 2015 in patients who died of iatrogenic Creutzfeldt-Jakob disease after being treated with cadaveric human growth hormone. This was followed by reports of early-onset CAA in patients who had childhood medical procedures using cadaveric dura mater, indicating that amyloid-beta transmission could lead to CAA later in life.
In 2024, Collinge and colleagues published a case series that suggested children treated with cadaver-derived pituitary growth hormone contaminated with amyloid-beta seeds developed changes consistent with Alzheimer's disease.
Taken together, findings from early studies suggest that amyloid transmission through transfused blood and blood products is a justifiable concern, Collinge and co-authors observed.
"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," they wrote in their Viewpoint. "Further research is essential for informing both this and future discussions and, therefore, is of strategic national and global importance."
This review identifies a knowledge gap, said Susan Kohlhaas, PhD, of Alzheimer's Research U.K. in Cambridge, England, who wasn't involved with the Viewpoint article.
"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," Kohlhaas wrote on the U.K. Science Media Center web site.
In previous research, the number of possible transmission cases was very small and the signal was only for CAA, noted Bart De Strooper, MD, PhD, of University College London, who also wasn't involved with the Viewpoint.
"That signal was small and would need to be confirmed through research -- we don't know yet that this is something that happens or that ought to be a concern, or that there would need to be any mitigation against," De Strooper wrote on the Science Media Center site.
"We do need more research in this area, but to make any parallels with prions is in my view premature and risks unwarranted public fear without the evidence to back it up," he stated. "It would be premature at this stage to worry about amyloid-beta transmission through blood transfusion -- we don't have convincing evidence."
Disclosures
Collinge reported holding a position as a senior investigator for the National Institute for Health and Care Research and is a director and shareholder of D-Gen. Co-authors reported relationships with government agencies, nonprofit groups, pharmaceutical companies, and others.
Kohlhaas had no conflicts of interest.
De Strooper reported relationships with Muna Therapeutics, Augustine Therapeutics, Eli Lilly, Biogen, Janssen Pharmaceuticals, Eisai, AbbVie, and other major pharmaceutical and biotechnology companies.
