Could aggregated Aβ seeds be passed from one person to another via blood transfusions? In the September 12 JAMA, researchers led by Jingcheng Zhao at Karolinska University Hospital in Solna, Stockholm, raised this alarming specter. In a retrospective study of more than one million medical records from Sweden and Denmark, they found that people who received blood from a person who went on to suffer multiple intracerebral hemorrhages were themselves at a threefold higher risk of having a brain bleed within the next few years. Because cerebral amyloid angiopathy is a main cause of such bleeds, the findings imply that aggregated amyloid in the donor's blood could potentially seed vascular deposits in the recipient, the authors argued. However, they acknowledged the evidence is indirect, since the medical records contained no information on CAA itself.
- Receiving blood from someone who had multiple brain bleeds upped a person’s risk of such a bleed.
- The results hint at a transmissible agent in blood that damages vasculature.
- β-amyloid is one possibility, but the relatively fast onset makes this less likely.
In an accompanying editorial, Steven Greenberg at Massachusetts General Hospital, Boston, noted additional reasons for skepticism. CAA usually takes decades to develop, not years, and would likely require a larger amount of seeding material than is found in blood. The existence of other transmissible agents that might damage vasculature should be explored, Greenberg wrote. Alzheimer’s researchers agreed. “This impressive and provocative study raises important questions that will stimulate necessary research on the mechanisms underlying vascular aging,” Lary Walker at Emory University, Atlanta, wrote to Alzforum (comment below).
Concern about the transmissibility of Aβ has grown in recent years, with reports of Aβ deposits forming in the brain and blood vessels of relatively young people who received pituitary growth hormone or dural grafts from older donors (Sep 2015 news; Jan 2016 news; Jan 2019 news). Some data even hint that Aβ seeds could be transferred on neurosurgical instruments, with a few people who had brain surgery as children developing CAA at an unusually young age (Feb 2018 news). A 2020 white paper recommended further studies to test the risk of transmission through surgery or donated blood (Sep 2020 news).
The current study is one fruit of that effort. Zhao and colleagues examined medical records from 759,858 people in Sweden who received a blood transfusion. After excluding patients who had an intracerebral hemorrhage (ICH) or other brain injury before transfusion, and those who received blood from someone who had already had an ICH, 558,032 participants remained. Of these, 503 received blood from someone who went on to have multiple ICHs within the next 20 years. During an average post-transfusion follow-up period of eight years, 18 of those 503 had a brain bleed. This represented a 3.2-fold higher incidence than seen in those who received blood from someone who later had one or no ICHs.
The findings replicated in a set of 329,512 medical records from Denmark. Among 210,663 participants who met the criteria, 249 received blood from someone who later had multiple ICHs, and six of those had a brain bleed themselves, a 2.8-fold higher risk. Overall, receiving blood from someone who later had multiple ICHs nudged up the cumulative risk of ICH by about 2 percent over 30 years, the researchers calculated.
The authors believe the findings point toward Aβ as the transmissible agent. They noted that recurrent ICH is highly associated with CAA. So is dementia, and notably, people who received blood from someone who had only a single ICH, but later developed dementia, also had a threefold higher risk of a brain bleed.
Alzheimer’s experts had doubts. David Werring at University College London noted that CAA accounts for only about a quarter of recurrent ICH cases. “This makes it difficult to know the type of underlying small-vessel disease the blood donor cohort had,” he wrote to Alzforum (comment below). Many thought the short time course made CAA less likely. “The relatively rapid appearance of ICH in recipients is inconsistent with seeded cerebral β-amyloidosis, which generally takes many years or decades to reveal itself in humans,” Walker wrote.
Overall, researchers emphasized the need for further study. “The results suggest there may be something transmissible in the blood … Aβ could well be the agent, but this has not been proven yet,” wrote Henrik Zetterberg at Gothenburg University, Sweden (comment below). For his part, Greenberg concluded, “The current study is not yet a reason for alarm, certainly not a reason to avoid otherwise indicated blood transfusion, but it is a strong call for more scientific digging.”—Madolyn Bowman Rogers
- Alzheimer’s Transmission Between People? Amyloid Plaques in Hormone Recipients Hint at Prion-like Spread
- News Brief: More Evidence for Aβ Spread Between People
- First In Vivo Look at Amyloidosis Sparked by Dural Grafts
- Can Aβ Seeds Be Transferred During Neurosurgery?
- Could Contaminated Scalpels Seed Amyloidosis?
- Meddling Medin: A Vascular Amyloid That Promotes CAA?
- Human Blood-Brain Barrier Model Blames Pericytes for CAA
- Confirmed: Human Pituitary Extract Linked to Amyloidosis Contains Aβ Seeds
- Peripheral Aβ Can Accumulate in Brain, Trigger Degeneration
- Diagnosis for Inflammation in Cerebral Amyloid Angiopathy
- Zhao J, Rostgaard K, Lauwers E, Dahlén T, Ostrowski SR, Erikstrup C, Pedersen OB, de Strooper B, Lemmens R, Hjalgrim H, Edgren G. Intracerebral Hemorrhage Among Blood Donors and Their Transfusion Recipients. JAMA. 2023 Sep 12;330(10):941-950. PubMed.
- Greenberg SM. Blood Transfusion and Brain Amyloidosis: Should We Be Worried?. JAMA. 2023 Sep 12;330(10):921-922. PubMed.