Preoperative Plasma Tau-PT217 and Tau-PT181 Are Associated With Postoperative Delirium

Abstract

Objective: This study aims to identify blood biomarkers of postoperative delirium. Background: Phosphorylated tau at threonine 217 (Tau-PT217) and 181 (Tau-PT181) are new Alzheimer disease biomarkers. Postoperative delirium is associated with Alzheimer disease. We assessed associations between Tau-PT217 or Tau-PT181 and postoperative delirium. Methods: Of 491 patients (65 years old or older) who had a knee replacement, hip replacement, or laminectomy, 139 participants were eligible and included in the analysis. Presence and severity of postoperative delirium were assessed in the patients. Preoperative plasma concentrations of Tau-PT217 and Tau-PT181 were determined by a newly established Nanoneedle technology. Results: Of 139 participants (73 ± 6 years old, 55% female), 18 (13%) developed postoperative delirium. Participants who developed postoperative delirium had higher preoperative plasma concentrations of Tau-PT217 and Tau-PT181 than participants who did not. Preoperative plasma concentrations of Tau-PT217 or Tau-PT181 were independently associated with postoperative delirium after adjusting for age, education, and preoperative Mini-Mental State score [odds ratio (OR) per unit change in the biomarker: 2.05, 95% confidence interval (CI):1.61-2.62, P < 0.001 for Tau-PT217; and OR: 4.12; 95% CI: 2.55--6.67, P < 0.001 for Tau-PT181]. The areas under the receiver operating curve for predicting delirium were 0.969 (Tau-PT217) and 0.885 (Tau-PT181). The preoperative plasma concentrations of Tau-PT217 or Tau-PT181 were also associated with delirium severity [beta coefficient (β) per unit change in the biomarker: 0.14; 95% CI: 0.09-0.19, P < 0.001 for Tau-PT217; and β: 0.41; 95% CI: 0.12-0.70, P = 0.006 for Tau-PT181). Conclusions: Preoperative plasma concentrations of Tau-PT217 and Tau-PT181 were associated with postoperative delirium, with Tau-PT217 being a stronger indicator of postoperative delirium than Tau-PT181.

Fascia iliaca compartment block can reduce the incidence of early post-operative cognitive impairment in elderly patients with high-risk hip replacement

“…Tau is the most abundant microtubule-associated protein and mainly binds to microtubule proteins to promote their polymerization to form microtubules, which are necessary to maintain the transport of substances between the neuronal cell cytosol and axons (Shen et al, 2016 ; Liang et al, 2022 ). In this study, the levels of Aβ and tau were significantly higher in group C than in group E on post-operative day 1 ( P < 0.01).…”

Digital detection of proteins

“…Spatial isolation of labels Detection of many single labels Enzymes confined in wells 8 or droplets 76 Microwell arrays 55,140 Wide FOV, high resolution multi-wavelength imaging 69 Amplification of nucleic acid labels in droplets 64 Arrays of droplets 77 Flow combined with laser-induced fluorescence 43 Labels directly associated with beads 60,63 Flow of droplets 59 Electrical 126 Nanoparticles 33, 103 Random dispersed arrays 62 Wide FOV plasmonic imaging 104 DNA nanostructures 127 Nanopore arrays 126 Scatter imaging 119 Laser induced fluorescence of bound labels 39 Flow cytometry 60 Coincidence detection 113 Laser induced fluorescence of released labels 42 Nanostructured surfaces 135 Time-resolved fluorescence (TIRF) microscopy 37 Particle motion 119,120 Mass spectrometry 142 Differential kinetics of specifically bound labels 123 Transmission electron microscopy 113 Nanopore blockade 125 Surface plasmon imaging 123 Nanopore translocation 127 Microbubbles 137 Diamond nitrogen vacancy centers 141 digital droplet immuno-PCR (ddIPCR). They formed oligonucleotide-labeled immunocomplexes at the surface of an ELISA plate, chemically released the label from the surface, partitioned the labels into droplets using a commercial droplet generator, performed PCR on the droplets, and then analyzed the on/off status of the droplets using a commercial droplet reader.…”

“…In one approach, the enhanced optical fields generated by nanostructures, such as microtoroid resonators 134 and nanoneedles, 135 can enable single molecule detection. For example, Liang et al 135 have reported a method for detecting p-tau captured on arrays of nanoneedles based on Poisson distribution analysis of enzyme labels bound to individual binding sites as described previously. 49,136 In this approach, individual immunocomplexes were labeled with HRP and precipitation of an insoluble product of the enzyme-substrate reaction changed the refractive index of the associated nanoneedle.…”

“…Outside of these 4 specific categories, other methods have been developed to enable single molecule detection of proteins for quantitative assays. In one approach, the enhanced optical fields generated by nanostructures, such as microtoroid resonators 134 and nanoneedles, 135 can enable single molecule detection. For example, Liang et al 135 have reported a method for detecting p-tau captured on arrays of nanoneedles based on Poisson distribution analysis of enzyme labels bound to individual binding sites as described previously.…”

The association between gut microbiota and postoperative delirium in patients

“…Changes from preoperative to postoperative day one plasma tau concentrations are associated with the severity of postoperative delirium and are higher in patients who develop postoperative delirium 19 . In previous studies the preoperative plasma concentrations of tau phosphorylated at threonine 217 (Tau-PT217), and threonine 181 (Tau-PT181) were associated with postoperative delirium in patients undergoing orthopedic surgery 20 . However, identifying the pathogenesis and biomarkers of postoperative delirium remain largely to be determined, impeding the progress of postoperative delirium research.…”