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Influence of Butyrylcholinesterase in Progression of Mild Cognitive Impairment to Alzheimer's Disease.
J Alzheimers Dis. 2018; 61(3):1097-1105.JA

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.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Gabriel AJ
Polytechnic Institute of Coimbra, ESTESC-Coimbra Health School, Biomedical Laboratory Sciences, Portugal. Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, Portugal.
Almeida MR
Neurogenetics Laboratory, Center for Neuroscience and Cell Biology, University of Coimbra, Portugal.
Ribeiro MH
Neurogenetics Laboratory, Center for Neuroscience and Cell Biology, University of Coimbra, Portugal. Laboratory of Neurochemistry, Coimbra University Hospital, Portugal. Faculty of Medicine, University of Coimbra, Portugal.
Carneiro D
Neurology Department, Coimbra University Hospital, Portugal.
Valério D
Neurology Department, Coimbra University Hospital, Portugal.
Pinheiro AC
Neurogenetics Laboratory, Center for Neuroscience and Cell Biology, University of Coimbra, Portugal.
Pascoal R
Laboratory of Neurochemistry, Coimbra University Hospital, Portugal.
Santana I
Neurology Department, Coimbra University Hospital, Portugal. Faculty of Medicine, University of Coimbra, Portugal.
Baldeiras I
Laboratory of Neurochemistry, Coimbra University Hospital, Portugal. Faculty of Medicine, University of Coimbra, Portugal.

MeSH

AgedAlzheimer DiseaseAmyloid beta-PeptidesApolipoproteins EBiomarkersButyrylcholinesteraseCognitive DysfunctionDisease ProgressionFemaleGenetic Predisposition to DiseaseHumansKaplan-Meier EstimateMaleMiddle AgedRisk Factorstau Proteins

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29254094

Citation

Gabriel, António José, et al. "Influence of Butyrylcholinesterase in Progression of Mild Cognitive Impairment to Alzheimer's Disease." Journal of Alzheimer's Disease : JAD, vol. 61, no. 3, 2018, pp. 1097-1105.
Gabriel AJ, Almeida MR, Ribeiro MH, et al. Influence of Butyrylcholinesterase in Progression of Mild Cognitive Impairment to Alzheimer's Disease. J Alzheimers Dis. 2018;61(3):1097-1105.
Gabriel, A. J., Almeida, M. R., Ribeiro, M. H., Carneiro, D., Valério, D., Pinheiro, A. C., Pascoal, R., Santana, I., & Baldeiras, I. (2018). Influence of Butyrylcholinesterase in Progression of Mild Cognitive Impairment to Alzheimer's Disease. Journal of Alzheimer's Disease : JAD, 61(3), 1097-1105. https://doi.org/10.3233/JAD-170695
Gabriel AJ, et al. Influence of Butyrylcholinesterase in Progression of Mild Cognitive Impairment to Alzheimer's Disease. J Alzheimers Dis. 2018;61(3):1097-1105. PubMed PMID: 29254094.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Influence of Butyrylcholinesterase in Progression of Mild Cognitive Impairment to Alzheimer's Disease. AU - Gabriel,António José, AU - Almeida,Maria Rosário, AU - Ribeiro,Maria Helena, AU - Carneiro,Diogo, AU - Valério,Daniela, AU - Pinheiro,Ana Cristina, AU - Pascoal,Rui, AU - Santana,Isabel, AU - Baldeiras,Inês, PY - 2017/12/20/pubmed PY - 2019/1/18/medline PY - 2017/12/20/entrez KW - Alzheimer’s disease KW - butyrylcholinesterase KW - disease progression KW - mildcognitive impairment SP - 1097 EP - 1105 JF - Journal of Alzheimer's disease : JAD JO - J Alzheimers Dis VL - 61 IS - 3 N2 - 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. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/29254094/Influence_of_Butyrylcholinesterase_in_Progression_of_Mild_Cognitive_Impairment_to_Alzheimer's_Disease_ DB - PRIME DP - Unbound Medicine ER -