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.