Under rare circumstances, Aβ seeds can be transferred to people during medical procedures. Researchers have turned up a few cases of tissue transplants or hormones from cadavers triggering amyloidosis in the brains or blood vessels of recipients. But could more common procedures, such as neurosurgeries or blood transfusions, spread proteopathic seeds? In a white paper in the September 16 Lancet Neurology online, a working group of 37 leading experts in the field, led by Bart De Strooper, U.K. Dementia Research Institute at University College London, conclude that existing data for this frightening vision are weak. They found 11 cases where neurosurgery is suspected of having sparked cerebral amyloid angiopathy decades later, and no cases of suspected transmission by blood transfusion.
- Working group finds little evidence that Aβ seeds are transferred during neurosurgery.
- Calls for long-term epidemiological study.
- Recommends neurosurgeons use separate tools for adults and children to minimize risk.
All the researchers agreed that the potential risk is so minuscule that it should not affect a person’s decision about whether to have neurosurgery. For context, about 14 million neurosurgeries are performed worldwide each year, according to the Program in Global Surgery and Social Change at Harvard Medical School (Dewan et al., 2018). “Our recommendation for anyone in need of neurosurgery or blood transfusion is to proceed as planned,” co-first author Elsa Lauwers, KU Leuven, Belgium, told Alzforum. “The potential risk, if any, will be outweighed by the benefit of the procedure.”
Other researchers concur. “The likelihood of transmission of Aβ seeds by neurosurgery or blood transfusion is negligible or very low in my view,” John Trojanowski at the University of Pennsylvania, Philadelphia, wrote to Alzforum. He was not part of the workshop.
Previously, researchers led by John Collinge and Sebastian Brandner at University College London had discovered that human growth hormone extracted from the pituitary glands of cadavers can transfer prion disease and brain amyloidosis to recipients (Sep 2015 news; Dec 2018 news). Collinge and Brandner are co-authors on the white paper. Likewise, co-author Charles Duyckaerts at Hôpital Pitié-Salpêtrière, Paris, as well as other groups, have found that grafts of postmortem dural tissue are associated with early onset amyloid plaques and CAA (Jan 2016 news; Hervé et al., 2018; Jan 2019 news). Physicians have stopped using material from cadavers, so this type of transmission is no longer a concern.
More ominously, perhaps, three papers in the last two years have suggested that Aβ seeds could travel from brain to brain by sticking to surgical instruments (Feb 2018 news; Hamaguchi et al., 2019; Giaccone et al., 2019). In most of the 11 reported cases, babies had undergone neurosurgery and developed severe CAA leading to brain hemorrhages in their 30s. These patients had no cognitive impairment, and only rarely developed parenchymal plaques or neurofibrillary tangles.
These case studies generated alarming headlines about the possibility of “transmissible Alzheimer’s” (Dec 2018 Nature; Feb 2019 Scientific American). The working group believes these fears are overblown. “The small number of documented cases and the retrospective nature of these studies preclude conclusions of a causal relationship,” they wrote. That said, they noted that because of the long latency period to CAA after exposure to seeds, additional cases could have been missed.
“Presently the data are not convincing enough that Aβ pathology has been transmitted by neurosurgical instruments,” co-author Mathias Jucker at the German Center for Neurodegenerative Diseases, Tübingen, wrote to Alzforum. Nonetheless, he believes the possibility exists and more investigation is needed.
To settle the issue, Lauwers, co-first author Giovanni Lalli, and colleagues suggest tracking people who have transfusions and neurosurgery early in life to evaluate whether they are more likely to have a neurodegenerative disease decades later. In addition, researchers should check for a history of neurosurgery in people with early onset CAA, noted co-author Stéphane Haïk at Hôpital Pitié-Salpêtrière, Paris.
Some of the authors plan to directly test for the presence of transmissible proteins on surgical tools. They will collect instruments that were used for neurosurgery on AD patients, and assess whether contact with those surfaces can trigger amyloidosis in mouse models of the pathology.
The authors recommend evaluating experimental procedures that might improve detection of proteopathic seeds. Methods that detect protein aggregation, such as the protein-misfolding cyclic-amplification assay and real-time quaking-induced conversion assay, could determine if seeds are present on surgical tools (Dec 2016 news; Sano et al., 2017; Groveman et al., 2018).
They call on the research community to find better ways of decontaminating equipment. Typical sterilization procedures, such as high temperatures and formaldehyde, are ineffective at removing misfolded proteins and may even stabilize them, but enzymes or other cleaning protocols might work (Edgeworth et al., 2011; Sep 2014 news). Ronald Melki at the French National Center for Scientific Research in Gif–sur–Yvette uses the detergent sodium dodecyl sulfate (SDS) to dissolve aggregates of Aβ42, tau, and α-synuclein from lab equipment, but he notes that the cleaning procedure has to be adapted to the particular polymorph (Fenyi et al., 2018).
Meanwhile, the authors recommend that neurosurgeons minimize any possible risk by using separate sets of instruments for children and older adults. Many clinics do this already, Lauwers noted. “It’s not a costly measure, and it won’t much change the daily practice in hospitals,” she said. Jucker said his hospital is now paying close attention to this issue.
Blood transfusions appear even safer than neurosurgery, the panel concludes. In one study of 1,465,845 people from Denmark or Sweden who received blood transfusions between 1968 and 2012, the 42,254 who got blood from someone later diagnosed with a neurodegenerative disease had no increased risk of getting the disease, compared to those who received blood from other donors (Edgren et al., 2016). This study was possible because blood banks in Denmark and Sweden store samples from each blood donation and track both donor and recipient health over decades (SCANDAT2 database).
Since there is no test for proteopathic seeds in blood, the authors recommend additional measures to minimize any possible risk to the blood supply. People with a family history of prion disease or an early onset neurodegenerative disorder, as well as anyone who received a dural graft or hormones from a cadaver, should be barred from donating blood. The authors do not recommend a maximum age limit for donors, as this would make it too difficult to maintain the blood supply. Adopting a blood banking system like Sweden and Denmark’s could help determine if there is any increased risk, they added.
Despite the apparent low risk of these medical procedures, the authors still believe caution is warranted. “It seems logical and good practice to adopt a series of proactive safety measures with good cost-to-potential-risk ratio,” they wrote.
They are distributing the white paper to hospitals and blood banks to raise awareness of the issue. “We want to make sure policy makers are well-informed and can make the best decision,” Lauwers said.—Madolyn Bowman Rogers
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