Plasma Myeloperoxidase as a Potential Biomarker of Patient Response to Anti-Dementia Treatment in Alzheimer’s Disease

Article type: Research Article

Authors: Wright, Joy R.^{a; b; 1} | Deen, Quazi Fahm E.^{c; 1} | Stevenson, Anna^d | Telford-Cooke, Leolie L.^e | Parker, Craig^f | Martin-Ruiz, Carmen^f | Steinert, Joern R.^g | Kalaria, Raj N.^h | Mukaetova-Ladinska, Elizabeta B.^{a; i; *}

Affiliations: [a] Department of Neuroscience, Psychology and Behaviour, University of Leicester, Leicester, UK | [b] Department of Cardiovascular Sciences, University of Leicester, Leicester, UK | [c] UCL Queen Square Institute of Neurology, University College London, London, UK | [d] School of Life Sciences, University of Glasgow, Glasgow, UK | [e] Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK | [f] BioScreening Core Facility-CAV, Newcastle University, Newcastle, UK | [g] Division of Physiology, Pharmacology and Neuroscience, University of Nottingham, UK | [h] Translational and Clinical Research Institute, Newcastle University, Newcastle, UK | [i] The Evington Centre, Leicester General Hospital, Leicester, UK

Correspondence: [*] Correspondence to: Prof. Elizabeta Mukaetova-Ladinska, Department of Neuroscience, Psychology and Behaviour, Maurice Shock Medical Sciences Building, University of Leicester, Leicester, LE1 7RH, UK. Tel.: +44 116 0116 373 6405; E-mail: eml12@leicester.ac.uk.

Note: [1] These authors contributed equally to this work.

Abstract: Background:Myeloperoxidase (MPO), a neutrophil-derived pro-inflammatory protein, co-localizes with amyloid-β (Aβ) plaques in Alzheimer’s disease (AD). Anti-dementia treatment may facilitate efflux of Aβ and associated plaque proteins from the brain to the peripheral circulation, therefore providing potential biomarkers for the monitoring of donor response to drug treatment. Objective:We investigated the diagnostic utility of MPO as a biomarker of AD, and how anti-dementia treatment alters plasma MPO concentration. Methods:Thirty-two AD patients were recruited, and plasma collected pre-drug administration (baseline), and 1- and 6-months post-treatment. All patients received cholinesterase inhibitors (ChEIs). At baseline and 6 months, patients underwent neuropsychological assessment. Forty-nine elderly healthy individuals with normal cognitive status served as controls. Plasma MPO concentration was measured by ELISA. Results:AD drug naïve patients had similar plasma MPO concentration to their control counterparts (p > 0.05). Baseline MPO levels positively correlated with Neuropsychiatric Inventory score (r = 0.5080; p = 0.011) and carer distress (r = 0.5022; p = 0.012). Following 1-month ChEI treatment, 84.4% of AD patients exhibited increased plasma MPO levels (p < 0.001), which decreased at 6 months (p < 0.001). MPO concentration at 1 month was greatest in AD patients whose memory deteriorated during the study period (p = 0.028), and for AD patients with deterioration in Cornell assessment score (p = 0.044). Conclusion:Whereas baseline MPO levels did not differentiate between healthy and AD populations, baseline MPO positively correlated with initial Neuropsychiatric Inventory evaluation. Post-treatment, transient MPO upregulation in ChEI-treated patients may reflect worse therapeutic outcome. Further studies are required to assess the potential of plasma MPO as an AD therapeutic biomarker.

Keywords: Alzheimer’s disease, biomarkers, cholinesterase inhibitors, inflammation, myeloperoxidase, plasma

DOI: 10.3233/JAD-220642

Journal: Journal of Alzheimer's Disease, vol. 89, no. 4, pp. 1483-1492, 2022