Blood tau-PT217 contributes to the anesthesia/surgery-induced delirium-like behavior in aged mice

INTRODUCTIONBlood phosphorylated tau at threonine 217 (tau-PT217) is a newly established biomarker for Alzheimer's disease and postoperative delirium in patients. However, the mechanisms and consequences of acute changes in blood tau-PT217 remain largely unknown. METHODSWe investigated the effects of anesthesia/surgery on blood tau-PT217 in aged mice, and evaluated the associated changes in B cell populations, neuronal excitability in anterior cingulate cortex, and delirium-like behavior using positron emission tomography imaging, nanoneedle technology, flow cytometry, electrophysiology, and behavioral tests. RESULTSAnesthesia/surgery induced acute increases in blood tau-PT217 via enhanced generation in the lungs and release from B cells. Tau-PT217 might cross the blood-brain barrier, increasing neuronal excitability and inducing delirium-like behavior. B cell transfer and WS635, a mitochondrial function enhancer, mitigated the anesthesia/surgery-induced changes. DISCUSSIONAcute increases in blood tau-PT217 may contribute to brain dysfunction and postoperative delirium. Targeting B cells or mitochondrial function may have therapeutic potential for preventing or treating these conditions.

Automated summary

Blood phosphorylated tau at threonine 217 (tau-PT217) is a biomarker for Alzheimer's disease and postoperative delirium. Anesthesia/surgery induced acute increases in blood tau-PT217 via enhanced generation in the lungs and release from B cells. Tau-PT217 might cross the blood-brain barrier, increasing neuronal excitability and inducing delirium-like behavior. Targeting B cells or mitochondrial function may have therapeutic potential for preventing or treating these conditions.