Wednesday, August 10, 2022

Alzheimer’s disease biomarkers may predict postoperative delirium

These data suggest that tau phosphorylation contributes to the development of post-delirium.

Zhongkong Xie, MD, PhD
Director, Geriatric Anesthesia Research Unit


Boston –
Clinical studies have demonstrated a strong association between Alzheimer’s disease (AD) and delirium. Alterations in tau protein, which can lead to brain entanglement, are one of the hallmarks of AD pathology, and tau phosphorylation at threonine 217 (tau-pT217) and threonine 181 (tau-pT181) are new plasma biomarkers. Which can detect early stage AD. A clinical study led by investigators at Massachusetts General Hospital (MGH) showed that plasma tau-pT 217 and tau-pT 181 are associated with the incidence and severity of postoperative delirium. conclusion . are published in history of surgery,

Preliminary studies by the same research group at MGH showed that the proportion of beta amyloid (which causes the signature plaques of AD) in the cerebrospinal fluid is associated with postoperative delirium. Recent studies in other laboratories have reported that plasma Tau-PT181 concentration differentiates AD dementia from other neurological disorders. Plasma levels of tau-pT217 are associated with changes in cerebrospinal fluid levels of tau-pT217 and AD development.

In this current study, MGH’s team, in collaboration with NanoMosaic (Woburn, MA), developed a new method to measure Tau-PT217 and Tau-PT181 concentrations in patients’ plasma, called the nanoneedle technique. “The nanoneedle technique is ultrasensitive, requires a small volume, and can measure low concentrations of molecules, including tau-pT 217 and tau-pt 181,” said lead author Fang Liang, MD, PhD, Department of Anesthesia, Serious Calls care and pain. The drug in MGH “integrates more than 20,000 nanoneedles onto silicon substrates assigned to a single analysis detection. Each nanoneedle is a single molecule biosensor functionalized with antibodies,” says Liang.

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The group conducted experiments on 139 patients who had had a knee replacement, hip replacement, or laminectomy (a type of back surgery) at MGH. They have found that preoperative plasma concentrations of tau-pT217 and tau-pT181 are associated with postoperative delirium. Furthermore, tau-pT217 is a stronger indicator of postoperative delirium than tau-pT181. “These results help in the diagnosis of postoperative delirium; identify intermediate outcomes that may facilitate clinical studies; and elucidate insights into potential mechanisms of postoperative delirium, ultimately leading to better and safer postoperative outcomes in patients.” leads,” says senior author Zhongkong Xie, MD, PhD, director of the Geriatric Anesthesia Research Unit in the MGH Department of Anesthesia, Critical Care. and pain medicine. Henry K. of Anesthesia at Zee Harvard Medical School. Beecher is also a professor. “These data also suggest that tau phosphorylation contributes, at least partially, to the development of postoperative delirium,” Xie says.

Co-author Oluwasen Akeju, chair of the Department of Anesthesia, Critical Care and Pain Medicine, says: “Postoperative delirium may be a clinical manifestation of preclinical AD and may serve as a useful early warning sign for patients.”

Higher preoperative plasma concentrations of tau-pT217 or tau-pT181 may predict the presence and severity of postoperative delirium, with tau-pT217 more strongly associated with these results. “We hope this work will spur further research to confirm these associations and to understand the mechanisms underlying the interaction of delirium and AD, ultimately leading to better interventions for both,” study co-authors The author Edward R. Marcantonio, MD, SM. from the Department of Medicine at Beth Israel Deaconess Medical Center. He is Professor of Medicine at Harvard Medical School.

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Additional co-authors are Katherine Baldiga, BS, Katherine Cody, MPH, and Jeanine Wiener-Kronish, MD, from the MGH Department of Anesthesia, Critical Care and Pain Medicine; Qimin Quan, PhD, from NanoMosaic, Yuan Shen, from MGH Department of Anesthesia, Critical Care and Pain Medicine and Anesthesia and Brain Research Institute, Shanghai Tenth People’s Hospital, Tongji University School of Medicine; Ashok Khatri, MS, and Shaun Choi, BS, from the MGH Endocrine Unit; and Brandon M. Westover, MD, from the MGH Department of Neurology.

The study was supported by the National Institutes of Health, which includes the National Institute on Aging and the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

About Massachusetts General Hospital
Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. Mass General Research Institute conducts the largest hospital-based research program in the country, with annual research operations of more than $1 billion and involving more than 9,500 researchers working in more than 30 institutions, centers and departments . In August 2021, Mass General was designated #4. US news and world report List of “Best Hospitals in America”.

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