2 From Bench to Bedside: How Tau Protein is Altered by Perioperative Factors

Abstract

Objective:Postoperative neurocognitive disorder is common after all forms of surgery in older adults. The mechanisms are multifactorial, and probably require pre-existing neuropathology, whether the patient is symptomatic or not. In Alzheimer's disease (AD) and other tauopathies, the microtubule-associated protein tau can undergo aberrant hyperphosphorylation potentially leading to the development of neurofibrillary pathology, one of the neuropathological hallmarks of the disease. Preclinical and human CSF studies suggest that anesthesia and surgery elicits an increment in CNS tauopathy, which may accelerate any preexisting neuropathology and produce a risk of delirium and the commonly reported changes in cognition.Participants and Methods:In this session, the author will present a bench to beside review of how tau protein is altered by perioperative factors and its potential relationship to the impairment of cognition after surgery and anesthesia. Published and ongoing studies will be reviewed to result in a discussion as to why changes in tau protein are concerning in perioperative disorders of cognition.Results:The presenter will initially review pre-clinical studies focusing on the impact of anesthetics and surgery-induced inflammation on tau pathology and how the impairment of resolution of surgery-induced inflammation, notably decreased lipoxin A4 signaling, is altered by aging, gender, or an increase in the tau pathology burden. These preclinical studies have partially informed a multi-center federally funded observational clinical study, currently in progress, involving neuroimaging to determine whether pre-operative CNS tauopathy, as reflected by PET imaging, predicts delirium and other cognitive and functional outcomes. This translational study will also examine whether anesthesia and spine surgery produces a longitudinal change in the brain tau burden in older adults, as compared to control, nonoperative patients.Conclusions:Bench to bedside research is needed in order to promote evidence-based care for patients at risk for ADRD.