Uncorrected Author Proof Journal of Alzheimer’s Disease xx (20xx) x–xx DOI 10.3233/JAD-170695 IOS Press 1 Influence of Butyrylcholinesterase in Progression of Mild Cognitive Impairment to Alzheimer’s Disease 1 2 3 Ant´ onio Jos´ e Gabriel a,b,∗ , Maria Ros´ ario Almeida c , Maria Helena Ribeiro c,d,f , Diogo Carneiro e , Daniela Val´ erio e , Ana Cristina Pinheiro c , Rui Pascoal d , Isabel Santana e,f and Inˆ es Baldeiras d,f 4 5 a Polytechnic Institute of Coimbra, ESTESC-Coimbra Health School, Biomedical Laboratory Sciences, Portugal 6 b Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, Portugal 7 c Neurogenetics Laboratory, Center for Neuroscience and Cell Biology, University of Coimbra, Portugal 8 d Laboratory of Neurochemistry, Coimbra University Hospital, Portugal 9 e Neurology Department, Coimbra University Hospital, Portugal 10 f Faculty of Medicine, University of Coimbra, Portugal 11 Handling Associate Editor: Beatrice Arosio 12 Accepted 16 October 2017 Abstract. 13 Background: Several demographic and genetic prognostic factors of conversion from mild cognitive impairment (MCI) to Alzheimer’s disease (AD) have been recognized so far. The most frequent polymorphism of butyrylcholinesterase (BuChE), the K-variant, has been proposed as a risk factor for AD, but data regarding its influence on early disease progression is still limited. 14 15 16 17 Objective: To investigate the influence of the BuChE-K variant in MCI progression to AD. 18 Methods: 96 MCI patients were included in the study and were genotyped for BuChE-K variant and Apolipoprotein E (ApoE). Cerebrospinal fluid (CSF) BuChE activity, as well as the levels of AD biomarkers amyloid- 42 (A 42 ), total and hyperphosphorylated tau (t-tau and p-tau) were also determined. 19 20 21 Results: No significant differences were found in either BuChE-K variant or BuChE activity between MCI patients that progressed to AD (MCI-AD) and patients that remained stable during clinical follow-up (MCI-St). As expected, baseline CSF levels of A 42 were significantly lower and t-Tau, p-Tau, and ApoE 4 allele frequency were significantly higher in MCI- AD patients. An association between the ApoE 4 allele and the BuChE-K variant in MCI-AD, but not in MCI-St patients, was found with patients carrying both alleles presenting the highest incidence of progression and the lowest estimated time of progression to AD. 22 23 24 25 26 27 Conclusion: Although BuChE-K alone does not seem to play a major role in progression to AD in MCI patients, a synergistic effect with the ApoE 4 allele was found, highlighting the importance of assessing these combined genotypes for evaluating risk progression in MCI patients. 28 29 30 Keywords: Alzheimer’s disease, butyrylcholinesterase, disease progression, mild cognitive impairment 31 ∗ Correspondence to: Ant´ onio Jos´ e Gabriel, ESTESC-Coimbra Health School, Biomedical Laboratory Sciences, Rua 5 de Outubro, S˜ ao Martinho do Bispo, Apartado 7006, 3046-854 Coimbra, Portugal. Tel.: +351 964464819; E-mail: agabriel@ estescoimbra.pt. ISSN 1387-2877/18/$35.00 © 2018 – IOS Press and the authors. All rights reserved