Tracheal aspirates of mechanically ventilated preterm infants possess cytopathic tau variants: a prospective exploratory study.

Tau protein, a microtubule-associated protein expressed in lung capillary endothelium, is detectable early in lung development and has been implicated in systemic dysfunction during adult respiratory infections. Its role in neonatal lung injury, however, remains undefined. In this study, we analyzed tracheal aspirates from 67 mechanically ventilated infants (51 preterm and 16 term) and compared them with 20 cord blood samples and five healthy adult plasma samples. Preterm infants were further stratified by histological chorioamnionitis status and severity of bronchopulmonary dysplasia (BPD) at 36-wk postmenstrual age (Jensen's 2019 criteria). Total tau concentrations were measured using a Meso Scale Discovery assay, and neuronal tau seeding assays assessed the presence of cytopathic tau variants. Tau was detected in all samples, with significantly higher concentrations in neonatal tracheal aspirates and cord blood compared with adult plasma. In both cord blood and tracheal aspirates, preterm infants exhibited elevated total tau levels relative to term infants. The tau protein present in preterm tracheal aspirates induced neuronal tau aggregation across gestational ages. Although total tau concentrations did not differ, the cytopathic activity of tracheal aspirates was increased in infants with chorioamnionitis. Neither total tau nor seeding activity correlated with BPD severity. Our study findings demonstrate that tau is abundant in the airways of mechanically ventilated preterm infants and exhibits cytopathic properties, suggesting a potential role in both neonatal lung injury and development. Further studies are needed to clarify the mechanistic contribution of tau to lung pathology in this highly vulnerable population.NEW & NOTEWORTHY In mechanically ventilated preterm infants, endogenous airway molecules may influence lung injury and development. Tau, a microtubule-associated protein expressed in lung endothelium, was abundant in neonatal tracheal aspirates and elevated in preterm infants. Tau in preterm samples also showed cytopathic seeding activity, which was further increased in infants with histological chorioamnionitis. These findings identify tau as a previously unrecognized bioactive airway component that may contribute to early lung pathology.