Critically ill patients rescued with extracorporeal membrane oxygenation (ECMO) are at risk for devastating complications, including stroke and intracerebral hemorrhage (ICH).¹ Despite an appreciation of some clinical risk factors, we cannot explain or predict neurologic complications, which occur in both venovenous (VV) and venoarterial (VA) ECMO, demonstrating a lack of mechanistic insight. The diagnosis of these complications in real time is challenging, potentially delaying timely intervention. We have previously shown that pneumonia elicits the pulmonary endothelium to produce cytotoxic variants of tau and amyloid-beta (Aβ) proteins that disseminate from the lungs and cause end-organ dysfunction, including the loss of long-term potentiation (persistent enhancement of synaptic transmission after hyperstimulation, necessary for learning and memory formation) in the hippocampus of mice.² In our pilot ECMO cohort, the presence of cytotoxic tau from oxygenator effluent correlated precisely with patients with pneumonia, was transmissible, and caused similar end-organ dysfunction; significantly higher tau levels were identified in oxygenators of patients who died, including 2 with ICH.³ In this follow-up study, we tested our hypothesis that higher circulating levels of Aβ and tau would be identified in adult ECMO patients with pneumonia and would be temporally associated with neurologic complications and death.