New! Sign up for our free email newsletter.
Science News
from research organizations

Alzheimer's disease biomarkers can predict postoperative delirium

Research also provides new mechanistic insights into how this delirium occurs

Date:
July 7, 2022
Source:
Massachusetts General Hospital
Summary:
A new study in patients reveals that two newly identified plasma biomarkers of Alzheimer's disease can predict postoperative delirium, one of the most common postoperative complications in older patients. The findings indicate the potential overlap between the mechanisms that cause Alzheimer's disease and postoperative delirium.
Share:
FULL STORY

Clinical studies have demonstrated a strong association between Alzheimer's disease (AD) and delirium. A change to the Tau protein, which can lead to the formation of tangles in brain, is one of the hallmarks of AD pathology, and Tau phosphorylation at threonine 217 (Tau-PT217) and threonine 181 (Tau-PT181) are new plasma biomarkers that can detect early-stage AD. A clinical study led by investigators at Massachusetts General Hospital (MGH) has shown that plasma Tau-PT217 and Tau-PT181 are associated with incidence and severity of postoperative delirium. The findings are published in Annals of Surgery.

Early studies from the same research group at MGH have shown that the ratio of beta amyloid (which causes AD's signature plaques) to Tau in cerebrospinal fluid is associated with postoperative delirium. Recent studies in other labs have reported that plasma Tau-PT181 concentration distinguishes AD dementia from other neurological disorders. Plasma levels of Tau-PT217 are associated with the changes in cerebrospinal fluid levels of Tau-PT217 and AD development.

In this current study, the team at MGH developed a novel method to measure Tau-PT217 and Tau-PT181 concentrations in plasma of patients, 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, PhD, in the Department of Anesthesia, Critical Care and Pain Medicine at MGH. "More than 20,000 nanoneedles are integrated on a silicon substrate assigned to detect one analyte. Each nanoneedle is a single molecule biosensor functionalized with antibodies," says Liang.

The group conducted experiments in 139 patients who had a knee replacement, hip replacement, or laminectomy (a type of back surgery) at MGH. They have discovered that preoperative plasma concentrations of Tau-PT217 and Tau-PT181 are associated with postoperative delirium. Moreover, Tau-PT217 is a stronger indicator of postoperative delirium than Tau-PT181. "These outcomes help diagnosis of postoperative delirium; identify intermediate outcomes that could facilitate clinical studies; and elucidate the insight into potential mechanisms of postoperative delirium, ultimately leading to better and safer postoperative outcomes in patients," says senior author Zhongcong Xie, MD, PhD, the director of the Geriatric Anesthesia Research Unit in the MGH Department of Anesthesia, Critical Care and Pain Medicine. Xie is also Henry K. Beecher Professor of Anesthesia at Harvard Medical School. "These data also suggest that Tau phosphorylation, contributes, at least partly, to the development of postoperative delirium," says Xie.

Adds co-author Oluwaseun Akeju, MD, chair of the Department of Anesthesia, Critical Care and Pain Medicine: "Postoperative delirium could be a clinical manifestation of preclinical AD and might serve as a useful early warning sign to patients."

High preoperative plasma concentrations of Tau-PT217 or Tau-PT181 can predict the presence and severity of postoperative delirium, with Tau-PT217 being the more strongly associated with these outcomes. "We hope this work will promote more research to confirm these associations and to understand further the mechanisms underlying the interaction of delirium and AD, ultimately leading to better interventions for both," says study co-author Edward R. Marcantonio, MD, SM, from the Department of Medicine at Beth Israel Deaconess Medical Center. He is a professor of Medicine at Harvard Medical School.

Additional co-authors are Kathryn Baldyga, BS, Kathryn 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 the 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 Shawn 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, including the National Institutes of Aging and the Eunice Kennedy Shriver National Institute of Child Health & Human Development.


Story Source:

Materials provided by Massachusetts General Hospital. Note: Content may be edited for style and length.


Journal Reference:

  1. Feng Liang, Kathryn Baldyga, Qimin Quan, Ashok Khatri, Shawn Choi, Jeanine Wiener-Kronish, Oluwaseun Akeju, Brandon M. Westover, Kathryn Cody, Yuan Shen, Edward R. Marcantonio, Zhongcong Xie. Preoperative Plasma Tau-PT217 and Tau-PT181 Are Associated With Postoperative Delirium. Annals of Surgery, 2022; Publish Ahead of Print DOI: 10.1097/SLA.0000000000005487

Cite This Page:

Massachusetts General Hospital. "Alzheimer's disease biomarkers can predict postoperative delirium." ScienceDaily. ScienceDaily, 7 July 2022. <www.sciencedaily.com/releases/2022/07/220707133739.htm>.
Massachusetts General Hospital. (2022, July 7). Alzheimer's disease biomarkers can predict postoperative delirium. ScienceDaily. Retrieved December 6, 2024 from www.sciencedaily.com/releases/2022/07/220707133739.htm
Massachusetts General Hospital. "Alzheimer's disease biomarkers can predict postoperative delirium." ScienceDaily. www.sciencedaily.com/releases/2022/07/220707133739.htm (accessed December 6, 2024).

Explore More

from ScienceDaily

RELATED STORIES