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

Abstract

AbstractINTRODUCTIONBlood 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.