PROJECT SUMMARY/ABSTRACT Patients in intensive care units are at high risk for long-term health threats including cognitive impairment. The correlation was only recently revealed after large-scale follow-up cognitive assessments on intensive patient survivors after their discharge from the hospital. There are testimonials, reviews and calls-to-action on many critical care websites and in journal issues over the last decade on this public health crisis. Studies have implicated delirium as a good predictor for long-term cognitive deficit; however, the causative and molecular mechanisms leading to abrupt cognitive impairment are unclear. In the past 4 years, our studies have discovered that patients in the intensive care unit who contracted bacterial pneumonia have elevated levels of cytotoxic amyloids in the bronchoalveolar lavage fluid, plasma, and the cerebrospinal fluid. Rodent brain slices incubated in the cerebrospinal fluids collected from bacterial pneumonia-positive patients show dampened hippocampal long-term potentiation. In comparison, synaptic strengthening is prominent in slices incubated in bacterial pneumonia-negative patients’ cerebrospinal fluid. Moreover, immunopurified from the cerebrospinal fluid or plasma using selective antibodies against Aβ and 𝜏 oligomers and injected into rodents, these cytotoxins induce neuronal dendritic spine retraction, reduce spine density, and impair animal learning. Our previous in vitro studies have implicated that in response to Pseudomonas aeruginosa infection, lung endothelium produces and releases cytotoxins including Aβ and 𝜏 species, and the cytotoxicity and bioactivity of these species are dependent upon the bacterial virulence. These endothelium-derived cytotoxins damage endothelial barrier integrity, hinder vascular repair following injury and, importantly, they are released into the systemic circulation in vivo. Thus, in this competitive renewal, the studies are designed to test the hypothesis that bacterial pneumonia-elicited lung endothelium-derived amyloids include pathological Aβ and 𝜏 species capable of dissemination and initiating aggregation. This work addresses a novel mechanism underlying the end organ dysfunction by systemically quantify cytotoxins released from endothelium in vitro, in rodents, and in patient specimens.