Lung endothelial cytopathic tau is sufficient to impair long-term potentiation during infection

Area of Science:

• Neuroscience
• Pulmonology
• Cell Biology

Background:

• Cytopathic tau variants are found in the lung, circulation, and brain after respiratory infections.
• The cellular origin of tau contributing to lung and brain injury during infection remains unclear.

Purpose of the Study:

• To investigate if lung capillary endothelium serves as a source of cytopathic tau during infection.
• To determine the role of endogenous tau in maintaining lung barrier integrity and its contribution to infection-induced brain injury.

Main Methods:

• Utilized a mouse model of sublethal Pseudomonas aeruginosa pneumonia.
• Assessed alveolar-capillary permeability and hippocampal long-term potentiation in wild-type and tau knockout mice.
• Examined the effects of restoring tau expression specifically in lung capillaries.

Main Results:

• Tau knockout mice exhibited higher alveolar-capillary permeability post-infection, indicating tau's role in lung barrier integrity.
• Infection impaired hippocampal long-term potentiation in wild-type mice but not tau knockout mice.
• Restoring tau expression in lung capillaries of knockout mice normalized barrier integrity and impaired hippocampal function.

Conclusions:

• Endogenous tau expressed in lung capillaries preserves alveolar-capillary barrier integrity during pneumonia.
• Lung capillary endothelial tau is a source of cytopathic tau that contributes to brain injury following respiratory infection.