Influence of Butyrylcholinesterase in Progression of Mild Cognitive Impairment to Alzheimer's Disease

J Alzheimers Dis. 2018;61(3):1097-1105. doi: 10.3233/JAD-170695.


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.

Keywords: Alzheimer’s disease; butyrylcholinesterase; disease progression; mildcognitive impairment.

MeSH terms

  • Aged
  • Alzheimer Disease / cerebrospinal fluid
  • Alzheimer Disease / genetics*
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Apolipoproteins E / genetics
  • Biomarkers / cerebrospinal fluid*
  • Butyrylcholinesterase / cerebrospinal fluid
  • Butyrylcholinesterase / genetics*
  • Cognitive Dysfunction / cerebrospinal fluid
  • Cognitive Dysfunction / genetics*
  • Disease Progression*
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Risk Factors
  • tau Proteins / cerebrospinal fluid


  • Amyloid beta-Peptides
  • ApoE protein, human
  • Apolipoproteins E
  • Biomarkers
  • tau Proteins
  • Butyrylcholinesterase