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Cytopathic tau injures the lung and brain, yet its cellular origin during infection is unknown. Here, we assessed whether lung capillary endothelium is a source of cytopathic tau that contributes to brain injury during infection. Alveolar-capillary permeability was higher in tau knockout than wild-type mice following sublethal Pseudomonas aeruginosa infection, indicating that endogenously expressed tau contributes to integrity of the lung\u2019s gas exchange unit. Hippocampal long-term potentiation was inhibited following sublethal infection in wild-type but not tau knockout mice, even though the blood-brain barrier was not overtly disrupted. Tau expression solely in lung capillaries of tau knockout mice was sufficient to restore alveolar-capillary barrier integrity and impair hippocampal long-term potentiation following sublethal infection. Thus, endogenous lung capillary endothelial tau preserves alveolar-capillary integrity, yet it is a source of cytopathic tau that injures the brain during pneumonia.<\/jats:p>","DOI":"10.1093\/ajrcmb\/aanag040","type":"journal-article","created":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T12:39:08Z","timestamp":1772541548000},"page":"1125-1141","source":"Crossref","is-referenced-by-count":2,"title":["Lung endothelial cytopathic tau is sufficient to impair long-term potentiation during infection"],"prefix":"10.1093","volume":"74","author":[{"given":"Mike T","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Physiology and Cell Biology, Center for Lung Biology, University of South Alabama , Mobile, AL,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikhail","family":"Alexeyev","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cell Biology, Center for Lung Biology, University of South 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