Early research from the identical analysis group at MGH have proven that the ratio of beta amyloid (which causes AD’s signature plaques) to Tau in cerebrospinal fluid is related to postoperative delirium.
In this present research, the workforce at MGH developed a novel methodology to measure Tau-PT217 and Tau-PT181 concentrations in plasma of sufferers, known as nanoneedle know-how, 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 creator Feng Liang, MD, PhD, within 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 performed experiments in 139 sufferers who had a knee substitute, hip substitute, or laminectomy (a kind of again surgical procedure) at MGH. They have found that preoperative plasma concentrations of Tau-PT217 and Tau-PT181 are related to postoperative delirium. Moreover, Tau-PT217 is a stronger indicator of postoperative delirium than Tau-PT181.
Alzheimer’s Disease and Postoperative Delirium
“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 creator Zhongcong Xie, MD, PhD , the director of the Geriatric Anesthesia Research Unit within the MGH Department of Anesthesia, Critical Care and Pain Medicine. Xie can also be Henry Okay. 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 extra strongly related to 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 research 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.