%0 Journal Article %J J Alzheimers Dis %D 2018 %T Influence of Butyrylcholinesterase in Progression of Mild Cognitive Impairment to Alzheimer's Disease. %A Gabriel, António José %A Almeida, Maria Rosário %A Ribeiro, Maria Helena %A Carneiro, Diogo %A Valério, Daniela %A Pinheiro, Ana Cristina %A Pascoal, Rui %A Santana, Isabel %A Baldeiras, Ines %K Aged %K Alzheimer Disease %K Amyloid beta-Peptides %K Apolipoproteins E %K Biomarkers %K Butyrylcholinesterase %K Cognitive Dysfunction %K Disease Progression %K Female %K Genetic Predisposition to Disease %K Humans %K Kaplan-Meier Estimate %K Male %K Middle Aged %K Risk Factors %K tau Proteins %X

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.

%B J Alzheimers Dis %V 61 %P 1097-1105 %8 2018 %G eng %N 3 %1 http://www.ncbi.nlm.nih.gov/pubmed/29254094?dopt=Abstract %R 10.3233/JAD-170695