Affiliations: [a] Polytechnic Institute of Coimbra, ESTESC-Coimbra Health School, Biomedical Laboratory Sciences, Portugal
| [b] Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, Portugal
| [c] Neurogenetics Laboratory, Center for Neuroscience and Cell Biology, University of Coimbra, Portugal
| [d] Laboratory of Neurochemistry, Coimbra University Hospital, Portugal
| [e] Neurology Department, Coimbra University Hospital, Portugal
| [f] Faculty of Medicine, University of Coimbra, Portugal
Correspondence:
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Correspondence to: António José Gabriel, ESTESC-Coimbra Health School, Biomedical Laboratory Sciences, Rua 5 de Outubro, São Martinho do Bispo, Apartado 7006, 3046-854Coimbra, Portugal. Tel.: +351 964464819; E-mail: [email protected].
Abstract: 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. Objective:To investigate the influence of the BuChE-K variant in MCI progression to AD. 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-β 42 (Aβ42), total and hyperphosphorylated tau (t-tau and p-tau) were also determined. 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 Aβ42 were significantly lower and t-Tau, p-Tau, and ApoE ɛ4 allele frequency were significantly higher in MCI-AD patients. An association between the ApoE ɛ4 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. 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 ɛ4 allele was found, highlighting the importance of assessing these combined genotypes for evaluating risk progression in MCI patients.
