Department of Anesthesiology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, China.
Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA.
Alzheimers Dement. 2023 Sep;19(9):4110-4126. doi: 10.1002/alz.13118. Epub 2023 May 30.
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.
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.
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.
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.
血液中磷酸化的苏氨酸 217 位tau（tau-PT217）是阿尔茨海默病和术后谵妄的新标志物。然而，血液 tau-PT217 急性变化的机制和后果在很大程度上仍不清楚。
我们研究了麻醉/手术对老年小鼠血液 tau-PT217 的影响，并使用正电子发射断层扫描成像、纳米针技术、流式细胞术、电生理学和行为测试评估了其与 B 细胞群、扣带回前部神经元兴奋性和谵妄样行为的相关变化。
麻醉/手术通过增强肺部的生成和 B 细胞的释放，导致血液 tau-PT217 的急性增加。tau-PT217 可能穿过血脑屏障，增加神经元兴奋性并诱导谵妄样行为。B 细胞转移和线粒体功能增强剂 WS635 减轻了麻醉/手术引起的变化。
血液 tau-PT217 的急性增加可能导致脑功能障碍和术后谵妄。靶向 B 细胞或线粒体功能可能具有预防或治疗这些疾病的治疗潜力。
