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

Abstract INTRODUCTION Blood 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. METHODS We 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. RESULTS 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. B cell transfer and WS635, a mitochondrial function enhancer, mitigated the anesthesia/surgery‐induced changes. DISCUSSION Acute 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.