title: Association between butyrylcholinesterase and cerebrospinal fluid biomarkers in Alzheimer's disease patients.
abstract: The deficit of cholinergic activity is one of the main findings in Alzheimer's disease (AD), and is related to the synthesis of acetylcholine, and the hydrolysing enzymes, acetylcholinesterase and butyrylcholinesterase (BuChE). Together with the Apolipoprotein E-ε4 allele (ApoE-ε4), the BuChE-K variant has been proposed to increase AD risk in certain populations. In addition, this polymorphism has been associated with a lower capacity to attenuate β-amyloid aggregation. In the present study we explored the interaction of the BuChE-K variant with its activity in CSF, conventional AD biomarkers and ApoE genotype. 217 AD patients and 200 age-matched controls were genotyped for the ApoE and the BuChE-K variant. BuChE activity in CSF, as well as the levels of the CSF-AD biomarkers amyloid-beta 42 (Aβ42), total and hyperphosphorylated tau (t-tau and p-tau) were determined in 88 of these patients. The results showed no significant differences in the BuChE-K variant distribution between patients and controls. No influence of the BuChE-K variant was seen neither in CSF BuChE activity, nor in the levels of Aβ42, t-tau and p-tau in AD patients. ApoE genotype also did not seem to influence CSF BuChE activity. Interestingly, in AD patients, an association between high CSF BuChE activity and increased levels of CSF Aβ42 was shown, particularly in ApoE-ε4 allele carriers. In our population, the BuChE-K variant does not seem to confer risk for AD or to influence the activity of the enzyme in CSF. However, we demonstrated an association between BuChE activity, ApoE-ε4 genotype and CSF Aβ42 levels, highlighting the importance of assessing BuChE activity as a possible modulator of Aβ load in the brain.
authors.affiliation: Instituto Politécnico de Coimbra, ESTESC-Coimbra Health School, Ciências Biomédicas Laboratoriais, Coimbra, Portugal; Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, Coimbra, Portugal. Electronic address: agabriel@estescoimbra.pt.
authors.forename: António José
authors.initials: AJ
authors.lastname: Gabriel
authors.affiliation: Neurogenetics Laboratory, Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
authors.forename: Maria Rosário
authors.initials: MR
authors.lastname: Almeida
authors.affiliation: Laboratory of Neurochemistry, Coimbra University Hospital, Coimbra, Portugal; Neurogenetics Laboratory, Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
authors.forename: Maria Helena
authors.initials: MH
authors.lastname: Ribeiro
authors.affiliation: Neurology Department, Coimbra University Hospital, Coimbra, Portugal.
authors.forename: João
authors.initials: J
authors.lastname: Durães
authors.affiliation: Neurology Department, Coimbra University Hospital, Coimbra, Portugal.
authors.forename: Miguel
authors.initials: M
authors.lastname: Tábuas-Pereira
authors.affiliation: Neurogenetics Laboratory, Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
authors.forename: Ana Cristina
authors.initials: AC
authors.lastname: Pinheiro
authors.affiliation: Laboratory of Neurochemistry, Coimbra University Hospital, Coimbra, Portugal.
authors.forename: Rui
authors.initials: R
authors.lastname: Pascoal
authors.affiliation: Neurology Department, Coimbra University Hospital, Coimbra, Portugal; Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
authors.forename: Isabel
authors.initials: I
authors.lastname: Santana
authors.affiliation: Laboratory of Neurochemistry, Coimbra University Hospital, Coimbra, Portugal; Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
authors.forename: Inês
authors.initials: I
authors.lastname: Baldeiras
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000201:enzymology* / Q000235:genetics; D019943:Amino Acid Substitution; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D001057:Apolipoproteins E / Q000235:genetics; D015415:Biomarkers / Q000134:cerebrospinal fluid; D002091:Butyrylcholinesterase / Q000134:cerebrospinal fluid* / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D015415:Biomarkers; D016875:tau Proteins; D002091:Butyrylcholinesterase
keywords: Alzheimeŕs disease; Amyloid-beta 42; Apolipoprotein E; Butyrylcholinesterase; Cerebrospinal fluid