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Detection of early-stage Alzheimer's pathology using blood-based autoantibody biomarkers in elderly hip fracture repair patients

DeMarshall, C; Oh, E; Kheirkhah, R; Sieber, F; Zetterberg, H; Blennow, K; Nagele, RG; (2019) Detection of early-stage Alzheimer's pathology using blood-based autoantibody biomarkers in elderly hip fracture repair patients. PLoS One , 14 (11) , Article e0225178. 10.1371/journal.pone.0225178. Green open access

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Abstract

Post-operative delirium (POD) is the most common complication following major surgery in non-demented older (>65 y/o) patients. Patients experiencing POD show increased risk for future cognitive decline, including mild cognitive impairment (MCI) and Alzheimer’s disease (AD) and, conversely, patients with cognitive decline at surgery show increased risk for POD. Here, we demonstrate that a previously established panel of AD-driven MCI (ADMCI) autoantibody (aAB) biomarkers can be used to detect prodromal AD pre-surgically in individuals admitted into the hospital for hip fracture repair (HFR) surgery. Plasma from 39 STRIDE (STRIDE: A Strategy to Reduce the Incidence of Postoperative Delirium in Elderly Patients) HFR patients and sera from 25 age- and sex-matched non-demented and non-surgical controls were screened using human protein microarrays to measure expression of a panel of 44 previously identified MCI aAB biomarkers. The predictive classification accuracy of the aAB biomarker panel was evaluated using Random Forest (RF). The ADMCI aAB biomarkers successfully distinguished 21 STRIDE HFR patients (CDR = 0.5) from 25 matched non-surgical controls with an overall accuracy of 91.3% (sensitivity = 95.2%; specificity = 88.0%). The ADMCI aAB panel also correctly identified six patients with preoperative CDR = 0 who later converted to CDR = 0.5 or >1 at one-year follow-up. Lastly, the majority of cognitively normal (CDR = 0) STRIDE HFR subjects that were positive for CSF AD biomarkers based on the A/T/N classification system were likewise classified as ADMCI aAB-positive using the biomarker panel. Results suggest that pre-surgical detection of ADMCI aAB biomarkers can readily identify HFR patients with likely early-stage AD pathology using pre-surgery blood samples, opening up the potential for early, blood-based AD detection and improvements in peri- and postoperative patient management.

Type: Article
Title: Detection of early-stage Alzheimer's pathology using blood-based autoantibody biomarkers in elderly hip fracture repair patients
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0225178
Publisher version: https://doi.org/10.1371/journal.pone.0225178
Language: English
Additional information: © 2019 DeMarshall et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/).
Keywords: Biomarkers, Alzheimer's disease, Cognitive impairment, Cerebrospinal fluid, Hemorrhagic fever with renal syndrome, Surgical and invasive medical procedures, Blood, Microarrays
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/10086602
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