Brain Proteins in Blood Transfusions
Research suggests blood transfusions may transmit harmful brain proteins like amyloid-beta, prompting calls for further study and safety measures. John Collinge, MD, and colleagues have reviewed evidence for transmitting amyloid-beta, a protein associated with Alzheimer's disease and cerebral amyloid angiopathy (CAA).
John Collinge, MD, and colleagues have suggested that blood transfusions could possibly transmit harmful brain proteins like amyloid-beta. According to Collinge, the risks of transfusion-related transmission of amyloid-beta pathology are currently undefined, and achieving clarity will take time.
Background
The Lancet Viewpoint article by Collinge and co-authors reviewed evidence for transmitting amyloid-beta, a protein associated with Alzheimer's disease and cerebral amyloid angiopathy (CAA). This was in response to 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.
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. 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.
Research Findings
Epidemiologic studies like this have inherent limitations, including the fact that detailed phenotyping to confirm CAA is not possible. However, the 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. 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.
Expert Opinion
Susan Kohlhaas, PhD, of Alzheimer's Research U.K. said that this review identifies a knowledge gap, and 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. Bart De Strooper, MD, PhD, of University College London, noted that the number of possible transmission cases was very small and the signal was only for CAA, and that it would be premature to worry about amyloid-beta transmission through blood transfusion without convincing evidence.
The need for further research is essential for informing discussions and is of strategic national and global importance, according to Collinge and co-authors. As stated by Collinge, 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. The potential risks associated with blood transfusions and the need for accurate screening assays are critical concerns that require immediate attention and further investigation.
