Cerebral amyloid angiopathy (CAA) is a progressive cerebrovascular and neurodegenerative condition marked by beta-amyloid accumulation in the walls of small brain vessels, which increases the risk of intracerebral hemorrhage (ICH), cognitive decline, and transient neurological episodes. Though the precise cause is uncertain, CAA is believed to involve abnormal processing of amyloid precursor protein (APP), which, when broken into beta-amyloid fragments, accumulates in vessel walls. Most cases are sporadic and associated with aging, but rare genetic and iatrogenic forms also exist, with iatrogenic cases linked to exposure to contaminated human tissue during medical procedures. Diagnosing CAA remains challenging, relying on Boston Criteria 2.0 and the Edinburgh Criteria for clinical and radiographic assessments of older adults with suspected CAA.
Emerging research suggests that beta-amyloid might exhibit prion-like transmissibility, as seen in studies where beta-amyloid seeded amyloidosis in animal models. The recent study by Zhao et al. found an elevated risk of ICH in recipients of blood from donors who later developed multiple spontaneous ICH events, prompting concerns that CAA might be transmissible via blood transfusion. While causality has not been confirmed, this study raises the question of transfusion-transmissible CAA, with significant implications for public health and blood donor screening procedures. Future research must address these concerns by replicating the Zhao et al. study, conducting case-control studies, and establishing prospective cohort studies to track transfusion recipients over time.
Research also highlights the need for rigorous study designs that use neuroimaging, plasma biomarkers, and neuropathology to increase specificity when identifying confirmed or probable CAA cases. Emerging technologies like machine learning and natural language processing could enhance data analysis and case identification across large radiological datasets. Plasma biomarkers may provide early risk indicators, offering a window into beta-amyloid accumulation before symptomatic CAA develops.
If CAA transmissibility through blood transfusion is confirmed, it would necessitate substantial changes to blood donor screening protocols, given CAA's potential public health impact. Further investigation is essential to clarify the role of transfusions in CAA transmission and to develop effective preventative measures for transfusion recipients.
