Acute Pseudomonas aeruginosa infection elicits production of cytotoxic t and Ab oligomers from pulmonary endothelium, and these amyloids accumulate in the BAL fluid of critically ill patients in the ICU (1–3). However, it remains unclear as to whether lung endothelial–derived amyloids access systemic tissues, and whether they contribute to end organ dysfunction. Accumulation of oligomeric t and Ab within the brain contributes to various forms of neuronal dysfunction, leading to learning and memory deficits (4). Because P. aeruginosa is a common cause of nosocomial pneumonia, and as patients with nosocomial pneumonia are at high risk of developing memory loss within the Alzheimer’s disease spectrum (5), we examined whether common gram-negative and gram-positive lung pathogens induce endothelial t and Ab oligomers that are sufficient to impair neurological function. Part of this work was previously published in abstract form (6).

Lung endothelial cells were infected with Klebsiella pneumonia and Staphylococcus aureus that had been isolated from the BAL fluid of intubated patients in the ICU. Supernatant was collected after bacterial infection (Figure 1A), prepared as described (1, 2), and incubated with brain endothelium. Lung endothelial supernatant generated in response to infection with both organisms induced intercellular gaps in brain endothelium (Figures 1B and 1C), and it contained transmissible and self-replicating t and Ab oligomers, as previously described (data not shown)(1, 2). Neutralizing t and Ab oligomers using T22 and A11 antibodies, respectively, abolished gap formation (Figures 1C and 1D). Amyloids were then eluted from the A11 antibody–bead complex, using a high-salt solution. Salt was removed by dialysis against Hanks’ balanced salt solution, and the antibody bound to amyloid denatured by boiling. The resulting fraction was applied to endothelial cells. These heat-stable amyloids