No Evidence to Suggest that the Use of Acetylcholinesterase Inhibitors Confounds the Results of Two Blood-Based Biomarker Studies in Alzheimer’s Disease

Article type: Research Article

Authors: Chiam, Justin Tao Wen^a | Lunnon, Katie^b | Voyle, Nicola^{c; e} | Proitsi, Petroula^{c; d} | Coppola, Giovanni^f | Geschwind, Daniel^f | Nelson, Sally^g | Johnston, Caroline^{c; d} | Soininen, Hilkka^h | Kłoszewska, Iwonaⁱ | Mecocci, Patrizia^j | Tsolaki, Magda^k | Vellas, Bruno^l | Hodges, Angela^{c; d} | Lovestone, Simon^{c; m} | Newhouse, Stephen^{c; d} | Dobson, Richard James Butler^{c; d} | Kiddle, Steven John^{c; e; 1} | Sattlecker, Martina^{c; d; 1; *}

Affiliations: [a] Guy’s, King’s and St Thomas School of Medical Education, King’s College London, London, UK | [b] Institute of Clinical and Biomedical Science, University of Exeter, Exeter, Devon, UK | [c] Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK | [d] NIHR Biomedical Research Centre for Mental Health and Biomedical Research, London, UK | [e] MRC Social, Genetic and Developmental Psychiatry Centre, King’s College London, London, UK | [f] Department of Neurology, Programme in Neurogenetics, David Geffen School of Medicine, University of California at Los Angeles, CA, USA | [g] SomaLogic, Boulder, CO, USA | [h] Department of Neurology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland | [i] Medical University of Lodz, Lodz, Poland | [j] Institute of Gerontology and Geriatrics, University of Perugia, Perugia, Italy | [k] 3rd Department of Neurology, “G. Papanicolaou” Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece | [l] INSERM U 558, University of Toulouse, Toulouse, France | [m] Department of Psychiatry, University of Oxford, Oxford, UK

Correspondence: [*] Correspondence to: Martina Sattlecker, NIHR Biomedical Research Centre for Mental Health South London and Maudsley NHS Foundation Trust & King’s College London, Institute of Psychiatry, De Crespigny Park, London, UK. Tel.: +44 20 7848 0236; [email protected]

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

Abstract: Background: There is an urgent need to discover Alzheimer’s disease (AD) biomarkers that are both easily measured and reliable. Research into blood-based biomarkers for AD using transcriptomics and proteomics has been an attractive and promising area of research. However, to date researchers have not looked into the possibility of AD medication being a confounding factor in these studies. Objective: This study explored whether acetylcholinesterase inhibitors (AChEIs), the main class of AD medication, are a confounding factor in AD blood biomarker studies. Methods: The most promising blood transcriptomic and proteomic biomarkers from two recent studies were analyzed to determine if they were differentially expressed between AD subjects on AChEIs and subjects that were not. Results: None of the gene or protein biomarkers analyzed were found to be significantly altered between subjects in either group. Conclusion: This study found no evidence that AChEIs are a confounding factor in these published AD blood biomarker studies. Further work is needed to confirm that this is also the case for other proposed biomarkers.

Keywords: Alzheimer’s disease, blood, cholinesterase inhibitors, gene expression, microarray, protein, proteomics

DOI: 10.3233/JAD-150289

Journal: Journal of Alzheimer's Disease, vol. 47, no. 3, pp. 741-750, 2015