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


Autoři: Cassandra DeMarshall aff001;  Esther Oh aff003;  Rahil Kheirkhah aff005;  Frederick Sieber aff004;  Henrik Zetterberg aff006;  Kaj Blennow aff006;  Robert G. Nagele aff001
Působiště autorů: Biomarker Discovery Center, New Jersey Institute for Successful Aging, Rowan University School of Osteopathic Medicine, Stratford, New Jersey, United States of America aff001;  Department of Geriatrics and Gerontology, Rowan University School of Osteopathic Medicine, Stratford, New Jersey, United States of America aff002;  Department of Medicine, Psychiatry and Behavioral Sciences, Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America aff003;  Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Bayview Medical Center, Baltimore, Maryland, United States of America aff004;  Graduate School of Biomedical Sciences (GSBS), Rowan University, Stratford, New Jersey, United States of America aff005;  Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden aff006;  Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden aff007;  Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, Queen Square, London, England, United Kingdom aff008;  UK Dementia Research Institute at UCL, London, England, United Kingdom aff009
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: 10.1371/journal.pone.0225178

Souhrn

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.

Klíčová slova:

Alzheimer's disease – Biomarkers – Blood – Cerebrospinal fluid – Cognitive impairment – Microarrays – Surgical and invasive medical procedures – Hemorrhagic fever with renal syndrome


Zdroje

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