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

• Published in: Journal of Alzheimer's disease Vol. 61; no. 3; p. 1097
• Main Authors: Gabriel, António José, Almeida, Maria Rosário, Ribeiro, Maria Helena, Carneiro, Diogo, Valério, Daniela, Pinheiro, Ana Cristina, Pascoal, Rui, Santana, Isabel, Baldeiras, Inês
• Format: Journal Article
• Language: English
• Published: Netherlands 01.01.2018
• Subjects: 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; mildcognitive impairment; butyrylcholinesterase; disease progression; Alzheimer’s disease
• ISSN: 1875-8908
• DOI: 10.3233/JAD-170695

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. To investigate the influence of the BuChE-K variant in MCI progression to AD. 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. 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. 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.