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Research also provides new mechanisms for understanding how this delirium occurs – ScienceDaily

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Clinical studies have shown a strong link between Alzheimer’s disease (AD) and delirium. Alteration of tau protein, which can lead to the formation of tangles in the brain, is one of the hallmarks of AD pathology, and tau phosphorylation at threonine 217 (Tau-PT217) and threonine 181 (Tau-PT181) are novel plasma biomarkers. which can detect early stage AD. A clinical trial led by Massachusetts General Hospital (MGH) researchers found that plasma Tau-PT217 and Tau-PT181 are associated with the frequency and severity of postoperative delirium. The findings are published in Annals of surgery.

Early studies by the same research group at MGH showed that the ratio of beta-amyloid (which causes the characteristic plaques of AD) to tau in the cerebrospinal fluid was associated with postoperative delirium. Recent studies in other laboratories have shown that plasma concentrations of Tau-PT181 distinguish AD dementia from other neurological disorders. Plasma Tau-PT217 levels are associated with changes in cerebrospinal fluid Tau-PT217 levels and the development of AD.

In this current study, a team at MGH developed a new method to measure the concentration of Tau-PT217 and Tau-PT181 in patients’ plasma, called nanoneedle technology, in collaboration with NanoMosaic (Woburn, MA). “The nanoneedle technology is ultrasensitive, requires a small volume, and can measure low concentrations of molecules, including Tau-PT217 and Tau-PT181,” says lead author Feng Liang, MD, of the Department of Anesthesia, Intensive Care, and Pain Medicine. at MGH. β€œMore than 20,000 nanoneedles are integrated into a silicon substrate designed to detect a single analyte. Each nanoneedle is a single-molecule biosensor functionalized with antibodies,” says Liang.

The team conducted experiments on 139 patients who underwent knee replacement, hip replacement or laminectomy (a type of back surgery) at MGH. They found that preoperative plasma concentrations of Tau-PT217 and Tau-PT181 were associated with postoperative delirium. Moreover, Tau-PT217 is a stronger predictor of postoperative delirium than Tau-PT181. “These results help diagnose postoperative delirium; identify intermediate outcomes that could facilitate clinical trials; and elucidate understanding of potential mechanisms of postoperative delirium, ultimately leading to better and safer postoperative patient outcomes,” says senior author Zhongkong Xie, MD. of Medical Sciences, MD, Director of the Geriatric Anesthesia Research Unit at the MGH Department of Anesthesia, Intensive Care, and Analgesia. Xie is also the Henry K. Beecher Professor of Anesthesia at Harvard Medical School. “These data also suggest that tau phosphorylation contributes, at least in part, to the development of postoperative delirium,” says Hsieh.

Adds co-author Oluwaseun Akeju, MD, chair of Anesthesia, Intensive Care and Pain Medicine, “Postoperative delirium may be a clinical manifestation of preclinical AD and may serve as a useful early warning signal for patients.”

High 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 outcomes. “We hope that this work will encourage additional research to confirm these links and further understand the mechanisms underlying the interaction between delirium and AD, ultimately leading to better interventions for both,” says study co-author Edward R. Marcantonio, MD, Medical Specialist, from the Department of Medicine, Beth Israel Deaconess Medical Center. He is a professor of medicine at Harvard Medical School.

Additional co-authors are Kathryn Baldiga, BSc, Kathryn Cody, M.H., and Jeanine Wiener-Cronisch, M.D., from MGH’s Department of Anesthesiology, Intensive Care and Analgesia; Timin Quan, PhD, of NanoMosaic, Yuan Shen of the Department of Anesthesia, Resuscitation, and Analgesia at MGH and the Anesthesia and Brain Research Institute of Shanghai Tenth People’s Hospital, Tongji University School of Medicine; Ashok Khatri, MS, and Shawn Choi, BS, of the Endocrine Department at MGH; and Brandon M. Westover, MD, of the Department of Neurology at MGH.

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

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